SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type

This is real experimental data — atoms placed by crystallography or cryo-EM, deposited by the people who did the experiment.

• THIS IS NOT A TARGET NOMINATION IN EITHER DIRECTION, and the reason is that this graph cannot currently sign the intervention. `mark-h3k9me3` argues H3K9 methylation restrains the fusion programme, so an inhibitor could worsen the leukaemia; `mechanism-h3k9me1-2-ctcf-balance-gates-kmt2a-rearrangement` argues H3K9me1/2 promotes rearrangement, so an inhibitor could be protective; and `gene-asb7`'s structure paper proposes a compound whose predicted effect is to RAISE SUV39H1. Three positions, two signs, one enzyme, and no measurement at the locus in any blood cell.
• Every published 'SUV39H1 inhibition' phenotype in AML rests on CHAETOCIN, which is a nonspecific histone lysine methyltransferase inhibitor (PMID 23416387, disputed by the original authors at PMID 23416388) and a thioredoxin-reductase-1 substrate and inhibitor whose selective anticancer effect is attributed to ROS (PMID 18999987), and has separately been called an HSP90 inhibitor (PMID 25742791). Two AML papers proposing SUV39H1 inhibition as a therapy (PMIDs 19881540, 25978433) are therefore not evidence about SUV39H1, and a beat reading them as such would nominate a target from a redox-active natural product.
• Essential-function toxicity is documented in the compartment that matters for a child. SUV39H1 organises pericentromeric heterochromatin and is required for faithful chromosome segregation in mitosis (PMID 22831836, title level), and loss of the upstream licensing ligase G2E3 causes aberrant euchromatic accumulation of SUV39H and widespread transcriptional repression (PMID 41094145). Neither a raise nor a lower stays at one CTCF element.
• The direction that looks safe is the one with the clearest documented harm elsewhere. Lowering SUV39H1 improves DNA repair and extends lifespan by 60% in a progeria mouse (PMID 23695662) - so 'lower H3K9me3' is beneficial in one genome-instability disease and predicted harmful in this one, and the two literatures have never been read against each other.
• The DSB result inverts the safety argument at the break itself. If CTCF-recruited SUV39H1, SETDB1 and HP1-gamma are what license accurate homologous-recombination repair at a break (PMID 42475683), then lowering H3K9 methylation prophylactically alongside etoposide or doxorubicin - the strategy this graph's rearrangement mechanism proposes with UNC0642 - would be removing the repressive-chromatin step at exactly the moment TOP2 breaks are being made. That is a mechanism by which the protective intervention could increase misjoining, and it is untested.
• SUV39H1 declines with normal ageing in HSCs (PMID 33037410), so every therapeutic argument about this axis in an infant is being made about a system whose baseline sits at the opposite end of the axis from most of the published data.

1. Does a menin inhibitor change H3K9me3 at menin-occupied genes in a KMT2A-rearranged cell? Menin delivers SUV39H1 in four endocrine systems, and removing menin from a promoter demonstrably removes SUV39H1 from it (PMID 30792230), yet no study in any system has measured H3K9me3 under a pharmacological menin inhibitor. The reagents are standard and the experiment is four ChIP-qPCRs per arm.
2. Is the menin SvID (aa 360-445) structurally separable from the MLL-binding cavity in a way that a co-structure would confirm? The 'distinct domains' conclusion rests on a truncation series plus the separately published menin/MLL structure, and no menin-SUV39H1 structure exists. If the surfaces are adjacent rather than distinct, a pocket inhibitor could perturb both.
3. Is SUV39H1 or SETDB1 the relevant H3K9me3 writer at a transcribed CTCF loop anchor? The two are separable on compartment - SUV39H1 goes pericentromeric, laminar and nucleolar, SETDB1 is non-pericentromeric and nucleolus-excluded - and neither has ever been measured at the KMT2A locus. One SETDB1 ChIP-seq track in K562 already in ENCODE answers half of it; the SUV39H1 half needs new work because the archive has none.
4. Does the writer reach the KMT2A anchor only through CTCF, and only after a break? That is the hypothesis this entry generates from PMID 42475683 and PMID 24927542, and it predicts that a resting-state H3K9me3 measurement at the element is the wrong assay - which would make Q108's RPE null uninformative rather than informative.
5. Does X-linkage matter here? SUV39H1 is at Xp11.23 and is the dominant H3K9 methyltransferase in the haematopoietic system, and nothing in this literature reports sex, X copy number or X-inactivation status - including in a CRISPR panel where those vary line to line.
6. Does the H3K14ub/G2E3 licensing layer explain the ASB7 circuit's mitotic gating instead of SUV39H1 degradation? Both mechanisms were published in 2025, both are cell-cycle gated, and neither cites the other's route.
7. Was writing this entry the right call at all, and what does its absence say about the corpus? The mark had an entry, the dispute had two mechanism entries and an analysis, and the enzyme had none - so the gap was in the argument rather than in the catalogue. The general question for the coordinator is whether any other mark entry in this graph has no writer entry behind it.

1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   SUV39H1 is UniProt O43463, entry name SUV91_HUMAN, 412 amino acids, primary gene name SUV39H1 with synonyms KMT1A and SUV39H, HGNC:11479 at Xp11.23, Ensembl ENSG00000101945; its feature table annotates a Chromo domain at 43-101, Pre-SET at 179-240, SET at 243-366 and Post-SET at 396-412, plus regions mediating interaction with SIRT1 (1-89) and MECOM (255-377), and it cross-references exactly one PDB entry, 3MTS. Its coded subcellular locations are Nucleus, Chromosome, Chromosome/centromere, Nucleus lamina and nucleoplasm, all ECO:0000269, with condition-specific phagosome-lumen and cell-membrane locations on Mycobacterium bovis infection.

   UniProtKB O43463 (SUV91_HUMAN) - Histone-lysine N-methyltransferase SUV39H1, Homo sapiens; with HGNC:11479 · UniProt Consortium; HUGO Gene Nomenclature Committee · UniProt Knowledgebase / HGNC 2026
   ▸What this evidence cannot show

   A single reviewed record was returned by gene_exact:SUV39H1 AND organism_id:9606 AND reviewed:true and its gene_primary was read back, so rules 62 and 65 are satisfied - but the paralogue SUV39H2 is 410 aa, two residues away, so the length assertion in this entry gives almost no protection against a swap and gene_primary is the only discriminator. The PDB cross-reference is recorded as an identifier only; no polymer entity was fetched, so nothing is claimed about what 3MTS covers.

   ▸Evidence that argues against this (2)

   • Rule 91: the coded evidence tells you a curator read an experiment, not that the paper is about the fact. The Nucleus lamina and nucleoplasm calls both rest on PubMed:23695662, which is a progeria study whose localisation content is that A-type lamins bind SUV39H1 and protect it from degradation - a protein-interaction result read as a compartment assignment. The nuclear-lamina label should not be quoted as an imaging survey of where this enzyme lives.
   • The feature table annotates no domain for the region that matters most to this graph's dispute, because no such region is known: there is no annotated locus-targeting element and no DNA-binding domain. Everything about where this enzyme goes is recruitment by a partner, which is why an absence of ChIP data is not repairable by inspecting the protein.
2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In MOUSE MLL-AF9-induced AML, SUV39H1 behaves as a tumour suppressor: SUV39H1 is down-regulated in a variety of leukaemias including MLL-r AML relative to normal individuals; decreased Suv39h1 expression AND decreased genomic H3K9me3 occupancy are both observed in leukaemia stem cells from MLL-r AML mouse models compared with hematopoietic stem/progenitor cells; Suv39h1 over-expression increases leukaemia latency and decreases LSC frequency while knockdown accelerates disease progression with more LSCs; and the transcriptional consequence is inactivation of Hoxb13 and Six1 and reversion of Hoxa9/Meis1 downstream targets. The paper also states that SUV39H1 is the dominant H3K9 methyltransferase in the haematopoietic system and that its expression declines with ageing.

   SUV39H1 regulates the progression of MLL-AF9-induced acute myeloid leukemia. · Chu Y, Chen Y, Guo H, Li M, et al. · Oncogene 2020
   PMID 33037410DOI
   ▸What this evidence cannot show

   Mouse MLL-AF9 MYELOID leukaemia, not human infant B-lineage KMT2A::AFF1 - rule 73. Abstract level: the H3K9me3 occupancy claim is genome-wide ('genomic H3K9me3 occupancy'), with no locus named, so it supports nothing about any particular gene and certainly nothing about the KMT2A locus. Over-expression is the gain-of-function arm, and a methyltransferase over-expression phenotype can act through non-histone substrates. Already cited once in this graph, in mark-h3k9me3 evidence[2].

   ▸Evidence that argues against this (2)

   • Two AML papers propose the OPPOSITE intervention. PMID 25978433 reports that the SUV39H1 inhibitor chaetocin induces CD11b expression and differentiation of AML cells at non-cytotoxic concentration, downregulates SUV39H1 and reduces H3K9me3 in HL-60 and KG-1a, synergises with SAHA and with JQ1, and does so in primary AML patient cells - concluding chaetocin may be effective for AML treatment. PMID 19881540 reports that SUV39H1 shRNA and chaetocin reactivate p15INK4B and E-cadherin in AML cells by H3K9 demethylation without promoter demethylation, and proposes H3K9 methyltransferases as therapeutic targets. So within AML the literature holds both 'SUV39H1 restrains the leukaemia' and 'inhibit SUV39H1 to treat the leukaemia', and this graph's H3K9 safety question is not a disagreement between our two entries alone.
   • The intervention arm of [E11] points the same way as the inhibitor papers in a completely different disease: depleting Suv39h1 RESTORES DNA repair capacity, delays senescence and extends lifespan by about 60% in Zmpste24-/- mice. A gene whose depletion is therapeutic in one model and oncogenic in another is not carrying a single sign.
3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   Menin interacts with SUV39H1 through a domain distinct from the one that binds MLL. Global H3K9 methylation, as well as H3K4 methylation, is decreased in Men1-/- MEF cells; menin interacts with SUV39H1 to mediate H3K9 methylation; N-terminal truncation mapping in 293T cells localises the interaction to menin amino acids 360-445, which the authors name the SUV39H1 interaction domain (SvID), and deletion beyond amino acid 360 abolishes binding; of four MEN1 patient-derived missense mutants inside the SvID - A411P, L413P, D418N and W436R - the mutants D418N and W436R are impaired in SUV39H1 binding; the authors state that their domain mapping together with the published menin/MLL structure indicate that distinct domains mediate SUV39H1 and MLL interactions, the MLL binding surface being the central cavity; menin, SUV39H1 and HDAC1 co-precipitate in one complex; and menin directly associates with the GBX2 promoter where menin-dependent recruitment of SUV39H1 is essential for chromatin remodelling and transcriptional regulation.

   Menin mediates epigenetic regulation via histone H3 lysine 9 methylation. · Yang YJ, Song TY, Park J, Lee J, et al. · Cell Death & Disease 2013
   PMID 23579270DOI
   ▸What this evidence cannot show

   Full text read (PMC3668625), not abstract only, and the domain numbers above are quoted from the Results text. Systems are 293T with transfected Myc-menin and GFP-SUV39H1 plus Men1-/- MEFs - no haematopoietic cell, no leukaemia, no fusion. The SvID is a truncation boundary from a deletion series, NOT a co-structure: no menin-SUV39H1 structure exists and the 'distinct domains' conclusion is an inference from the truncation series plus the separately published menin/MLL structure. Two of the four patient mutants inside the window did NOT affect binding, which is the correct specificity control and also limits how much the domain assignment can bear. Confidence is moderate rather than strong because the load-bearing interaction data are tagged-overexpression IPs.

   ▸Evidence that argues against this (2)

   • The strongest argument against reading this as relevant to KMT2A::AFF1 is that the whole menin-SUV39H1 literature is endocrine. Four independent replications exist and every one is in beta cells, islet tumour cells, neuroendocrine tumour lines or fetal pancreatic progenitors; menin's documented H3K9me3 target promoters are GBX2, IL-6, MME and Ins1. No study has asked whether menin delivers SUV39H1 anywhere in a haematopoietic cell, let alone at a KMT2A fusion target.
   • It cuts against its own use as a menin-inhibitor warning in one specific way: if the SvID really is a distinct surface, then a pocket-binding menin inhibitor is NOT predicted to compete SUV39H1 off menin. The warning this entry carries depends on the separate chromatin-eviction argument from PMID 30792230, not on competition, and those two mechanisms would be distinguished by a menin-inhibitor co-IP - which nobody has published.
4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   The menin-SUV39H1 axis replicates in four further papers, all in endocrine systems, and one of them demonstrates that removing menin from a promoter removes SUV39H1 from it. Menin occupies the IL-6 promoter and recruits SUV39H1 to induce H3K9 methylation, with H3K9 and not H3K27 or H3K4 methylation mediating menin-dependent IL-6 regulation in mouse islet tumour cells (PMID 25088994). Menin and Daxx interact directly and are both required to enhance H3K9me3 at the MME promoter as mediated partly by SUV39H1, and the NET-associated menin T429K mutant reduces Daxx binding, MME repression and NET cell proliferation (PMID 27872097). GLP-1-activated PKA phosphorylates menin at Ser487, which increases menin's binding to nuclear actin/myosin IIa and sequesters it from the Ins1 promoter, leading to REDUCED binding of SUV39H1 and HDAC1 at that locus and increased Ins1 transcription (PMID 30792230). And HIP/AKT-mediated repression of FOXO1 suppresses menin expression, reducing menin binding at three proislet transcription-factor promoters, decreasing SUV39H1 recruitment and thus reducing repressive H3K9me3 there (PMID 29716892).

   GLP-1 signaling suppresses menin's transcriptional block by phosphorylation in β cells. · Xing B, Ma J, Jiang Z, Feng Z, et al. · The Journal of Cell Biology 2019
   PMID 30792230DOI
   ▸What this evidence cannot show

   Abstract level for all four. The citation block is the Ser487 paper because it is the one carrying the load-bearing mechanism - menin off the promoter means SUV39H1 off the promoter - and the other three PMIDs are named in the claim rather than given their own citation blocks. Two of the four (PMIDs 30792230 and 29716892) share a senior-author group with each other, and PMIDs 23579270 and 25088994 share one, so the four papers are three independent groups at most. Every system is endocrine; none is haematopoietic; none involves a fusion protein.

   ▸Evidence that argues against this (2)

   • The replication is of the AXIS, not of a genomic address relevant here, and the four target promoters have nothing in common with each other or with a KMT2A fusion target. A recruiter that delivers a methyltransferase to IL-6, MME, Ins1, GBX2 and three proislet transcription factors across four tissues looks like a general property of menin-occupied chromatin, which weakens any prediction about a specific locus and strengthens only the general warning about menin eviction.
   • None of the four uses a pharmacological menin inhibitor. The eviction argument is built on phosphorylation-driven sequestration and on MEN1 knockout, and a revumenib-class inhibitor displaces the menin-MLL contact rather than the whole protein - so the predicted effect on SUV39H1 delivery could be smaller than these papers imply, or absent.
5. E5strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   The PAF1 complex recruits SUV39H1. Parafibromin/CDC73, a component of the RNA polymerase II-associated PAF1 complex, interacts with SUV39H1; the central region of parafibromin, amino acids 128-227, is required both for that interaction and for transcriptional repression; parafibromin associates with the promoter and coding regions of cyclin D1 and is required for the recruitment of SUV39H1 and the induction of H3K9 methylation but NOT H3K4 methylation there; and RNA interference shows SUV39H1 is critical for cyclin D1 repression. Separately, SHP2 dephosphorylates parafibromin, after which it stably binds beta-catenin and the parafibromin/beta-catenin interaction OVERRIDES parafibromin/SUV39H1-mediated transrepression, inducing cyclin D1 and c-myc.

   The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression. · Yang YJ, Han JW, Youn HD, Cho EJ · Nucleic Acids Research 2010
   PMID 19906718DOI
   ▸What this evidence cannot show

   Abstract level for both papers; the SHP2 half is PMID 21726809 (Mol Cell 2011) and is named in the claim rather than carrying its own citation block. Neither paper is in a haematopoietic cell and neither involves a KMT2A fusion. The target is cyclin D1, and the PAF1c subunit doing the recruiting is CDC73, not PAF1 itself - so this is a statement about one subunit's side activity, not about the complex as a whole. This entry's relevance argument depends on a separate fact established elsewhere in this graph, that PAF1c is required for fusion localisation.

   ▸Evidence that argues against this (2)

   • The sibling result in this graph is PAF1c recruiting SETDB1, not SUV39H1, at Meis1 and Hoxa9 in MLL-AF9 cells (PMID 29774127, cited in gene-cdc73, gene-paf1 and mark-h3k9me3). So where the leukaemia measurement exists, the writer CDC73 brings is SETDB1 - which argues that SUV39H1's PAF1c route is the non-haematopoietic one, and that reading the cyclin D1 result across into this disease would put the wrong enzyme at the fusion's targets.
   • The SHP2 result means the same CDC73 phospho-state that licenses SUV39H1 recruitment also licenses beta-catenin binding when reversed, so a RAS-pathway signal upstream can flip the sign of this recruitment without any change in SUV39H1 itself. In a disease where RAS-pathway co-mutations are common, that makes any prediction from this axis conditional on a lesion this entry does not model.
6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In U2OS osteosarcoma and HEK-293T cells, CTCF recruits the H3K9 machinery to double-strand breaks. CTCF recruits the repressive chromatin proteins HP1-gamma, KAP1, SUV39H1, SETDB1 and KDM5A, thereby enabling rapid accumulation of BRCA1/BARD1 at DSBs; CTCF depletion abrogates the enrichment of these repressive chromatin proteins with loss of H3K9 methylation and H3K4 demethylation at DSBs and defective rapid BRCA1/BARD1 recruitment; depriving any one component, or deregulating H3K9 methylation/H3K4 demethylation, compromises the immediate accumulation of the others as well as of BRCA1/BARD1; and the consequence is abrogated EXO1/DNA2 recruitment, defective DNA end resection and dysfunctional homologous recombination. The authors describe CTCF as establishing a hierarchical recruitment cascade in HR.

   CTCF primes repressive chromatin for rapid BRCA1/BARD1 recruitment to drive homologous recombination repair of DNA double-strand breaks. · Hwang SY, Choi D, Choi MJ, Jo HR, et al. · Nucleic Acids Research 2026
   PMID 42475683DOI
   ▸What this evidence cannot show

   Abstract plus Materials and methods read from PMC13384258. The systems are HEK-293T and U2OS-based DSB reporter lines - AsiSI-ER-U2OS, ER-mCherry-LacI-FokI-DD-U2OS, DR-GFP and EJ5-GFP - so every break is enzyme-induced at a reporter or at AsiSI sites, NOT at the KMT2A locus, and nothing here is a blood cell. The reagent list includes etoposide and BIX-01294, which is a G9a/GLP inhibitor, so the H3K9-deregulation arm is partly pharmacological with a compound whose selectivity is the same class of question this graph already asks about UNC0642. The HP1 paralogue named is HP1-gamma/CBX3, not HP1-alpha/CBX5, and this entry does not transfer it. A 2026 paper with no replication known to this project.

   ▸Evidence that argues against this (2)

   • The direction is the opposite of the one this graph's rearrangement mechanism needs. Here repressive chromatin at a break PROMOTES accurate repair by homologous recombination, so H3K9 methylation is protective of genome integrity at the break - whereas mechanism-h3k9me1-2-ctcf-balance-gates-kmt2a-rearrangement has H3K9me1/2 accumulation at the KMT2A BCR as the state that PRECEDES rearrangement. Both can be true only if the relevant marks or the relevant timing differ, and neither has been measured at this locus.
   • It also undercuts its own use as an explanation of the KMT2A anchor. In a G1 or non-cycling cell, or in a lymphoid progenitor where HR is not the dominant pathway for a TOP2 break, a cascade whose readout is BRCA1/BARD1-dependent resection may simply not run, and the infant disease's putative cell of origin is a fetal progenitor, not a cycling osteosarcoma line.
7. E7strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   A KAP1/HP1/SUV39H1 complex is rapidly loaded onto chromatin at double-strand breaks; suv39h1 methylates H3K9 there, facilitating loading of additional kap-1/HP1/suv39h1 through the chromodomain of HP1 binding nascent H3K9me3, which initiates cycles of loading and methylation that spread H3K9me3 and the complexes for tens of kilobases from the break; these H3K9me3 domains activate the Tip60 acetyltransferase, which acetylates ATM and histone H4; cells lacking suv39h1 show defective Tip60 and ATM activation, decreased DSB repair and increased radiosensitivity; and activated ATM phosphorylates kap-1, releasing the repressive complex from chromatin as a negative feedback loop.

   DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin. · Ayrapetov MK, Gursoy-Yuzugullu O, Xu C, Xu Y, et al. · Proceedings of the National Academy of Sciences 2014
   PMID 24927542DOI
   ▸What this evidence cannot show

   Abstract level; the cell systems are not named in the abstract. The HP1 paralogue is not specified, so this cannot be attributed to CBX5, CBX1 or CBX3. The mechanism is explicitly TRANSIENT, with ATM-driven release, which means any single-timepoint occupancy measurement can miss it entirely - and every H3K9 measurement in this graph is a single timepoint in unirradiated cells. 'Tens of kilobases' of spreading is larger than the whole 7,466 bp KMT2A breakpoint cluster region, so if this applies at the KMT2A locus it would not be resolvable as a BCR-versus-flank contrast at all.

   ▸Evidence that argues against this (2)

   • It argues that H3K9me3 at a break is a CONSEQUENCE of breakage rather than a determinant of it, which is the reading that would dissolve this graph's dispute in the least interesting way: both entries would be describing a downstream mark. Against that, the founding rearrangement paper's H3K9me1 changes are produced by KDM3B depletion in undamaged cells and precede the cytogenetic event, so at least the me1 arm is not purely a damage response.
   • A negative feedback loop that strips the complex off chromatin as soon as ATM activates also predicts that an H3K9me3 ChIP in a cell population with asynchronous damage sees a small, averaged-out signal - so a null result at a break-prone element is weak evidence of absence, and Q108's RPE null should not be read as one.
8. E8established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   ENCODE holds no released ChIP-seq experiment for SUV39H1 or SUV39H2 in any biosample, while the rest of the H3K9 machinery is represented: SETDB1 5 experiments (K562 x3, HepG2, HEK293), CBX5 4 (K562, GM12878, H1, HepG2), CBX1 2 (K562, HepG2), CBX3 4 (K562 x2, GM12878, HCT116), EHMT2 3 (K562, A549, HepG2) and TRIM28 5 (K562 x3, HEK293 x2). So the writer at the centre of this graph's H3K9 dispute is the one member of the machinery for which the archive route is structurally unavailable, in every cell type.

   ENCODE Portal experiment search, assay_title=TF ChIP-seq, status=released, per target label · ENCODE Project Consortium · ENCODE Portal 2026
   ▸What this evidence cannot show

   This bounds ENCODE and nothing else. Individual-lab depositions in GEO were NOT swept for SUV39H1 ChIP-seq, so the correct absence class for the archive half is measured-not-searched rather than never-measured, and one GEO query could change it. 'TF ChIP-seq' is the assay title under which these proteins are filed; a SUV39H1 experiment filed under a different assay title would be missed by this exact query.

   ▸Evidence that argues against this (1)

   • An archive absence is an absence of one archive, and it is the weakest kind of bound this project recognises. The companion literature bound is also titles-and-abstracts only (rule 80), so a SUV39H1 ChIP-seq track covering chr11:118.4 Mb could exist today in a GEO deposition attached to a paper about something else, and both of this entry's bounds would be blind to it.
9. E9strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In LEUKAEMIA cells, SUV39H1 has exactly one named genomic address: the rDNA locus, reached through PHF6. PHF6 binds H3K9me3 and H3K27me1 on nucleolar chromatin and recruits SUV39H1 to the rDNA locus; PHF6 deletion decreases SUV39H1 recruitment to rDNA gene loci, reducing H3K9me3 and promoting rDNA transcription; knockdown of either SUV39H1 or PHF6 attenuates the H3K9me3 increase and rDNA repression produced by over-expressing the other, establishing interdependence; PHF6 clinical mutants impair SUV39H1 binding and recruitment with increased rDNA transcription and increased leukaemia cell proliferation in vitro and xenograft growth in vivo; and AML patients with mutated PHF6 have elevated pre-rRNA.

   PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia. · Tsai HI, Wu Y, Huang R, Su D, et al. · Acta Pharmaceutica Sinica B 2022
   PMID 35847518DOI
   ▸What this evidence cannot show

   Abstract level. The disease context is PHF6-mutant AML and T-ALL, not KMT2A-rearranged leukaemia, and PHF6 mutation is not a recurrent lesion in infant KMT2A::AFF1. The title as published contains a typographical error ('muntant'), reproduced here verbatim because the citation checker compares stored title against the fetched title. rDNA is a repeat array, so an occupancy claim there rests on multi-mapping reads and the abstract does not state how that was handled.

   ▸Evidence that argues against this (2)

   • It argues the wrong compartment for this graph. The nucleolus is where SUV39H1's only locus-resolved leukaemia address sits, and UniProt records the OTHER H3K9me3 writer, SETDB1, as excluded from nucleoli - so if the relevant writer at a transcribed euchromatic loop anchor is one of the two, this result points away from SUV39H1 rather than towards it.
   • This graph already carries an rDNA re-mapping proposal for a different reason, and a reader could mistake this paper for support for it. It is not: PHF6-SUV39H1 at rDNA is a separate mechanism in a different genotype, and nothing here connects rDNA H3K9me3 to a KMT2A fusion.
10. E10moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    In human AML lines, SUV39H1 has been placed by ChIP at two named gene promoters, and the intervention proposed there is inhibition. In AML cells with hypermethylated p15INK4B and E-cadherin promoters, the DNMT inhibitor 5-aza-2'-deoxycytidine induced both genes and decreased DNA methylation, H3K9 methylation AND the amount of SUV39H1 associated with those promoters; SUV39H1 shRNA and chaetocin induced p15INK4B and E-cadherin expression with H3K9 demethylation and no promoter demethylation; and the authors conclude that reactivation required H3K9 demethylation achieved directly by inhibiting SUV39H1 expression or activity, highlighting H3K9 methyltransferases as therapeutic targets for reactivating hypermethylated genes.

    Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. · Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR · Oncogene 2010
    PMID 19881540DOI
    ▸What this evidence cannot show

    Abstract level; the AML lines are not named in the abstract and the fusion status of the cells is not stated, so this is not a KMT2A-rearranged result. Half the pharmacology is chaetocin, whose non-selectivity is [E14] and [E15], and the shRNA arm is what carries the genetic claim. Confidence moderate because the locus-level occupancy claim is a ChIP in a cell line at two promoters with no genome-wide context.

    ▸Evidence that argues against this (1)

    • It contradicts [E2] in direction within the same disease family: here SUV39H1 silences tumour suppressors in AML and should be inhibited, there SUV39H1 restrains MLL-AF9 leukaemia and should be raised. Neither paper measures the other's endpoint, and until one does, this graph cannot state a sign for SUV39H1 manipulation in AML at all - which is a stronger and more honest position than either entry currently in the graph takes.
11. E11strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    SUV39H1 protein abundance is set by proteasomal degradation and by a lamin interaction, and depleting it is beneficial in one disease model. A-type lamins interact with SUV39H1; prelamin A/progerin binds SUV39H1 more strongly and protects it from proteasomal degradation, consequently increasing H3K9me3 levels; depletion of Suv39h1 reduces H3K9me3, restores DNA repair capacity and delays senescence in progeroid cells; and loss of Suv39h1 in Zmpste24-/- mice delays body-weight loss, increases bone mineral density and extends lifespan by about 60%.

    Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. · Liu B, Wang Z, Zhang L, Ghosh S, et al. · Nature Communications 2013
    PMID 23695662DOI
    ▸What this evidence cannot show

    Abstract level. The disease model is Hutchinson-Gilford progeria / Zmpste24-/- mice - nothing haematopoietic, nothing leukaemic. This is also the paper UniProt's Nucleus lamina localisation call rests on, so the compartment assignment and the degradation mechanism come from the same source and are not independent of each other.

    ▸Evidence that argues against this (2)

    • It is a third, independent degradation control on the same enzyme, which weakens rather than strengthens any enzyme-activity model of H3K9me3 at a locus: with CUL5-ASB7 degrading it, lamin A protecting it and G2E3/H3K14ub licensing where it goes, an experiment that perturbs a methyltransferase or demethylase and reads H3K9me3 has at least three uncontrolled routes to the same readout.
    • The sign here opposes [E2] and agrees with [E10]: less SUV39H1 means better DNA repair. If that generalises even partly to a haematopoietic cell, then 'raise H3K9me3 to restrain the fusion' and 'lower H3K9me3 to protect the genome' are competing objectives in the same patient.
12. E12strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Where SUV39H goes is licensed by a separate ubiquitin mark and is cell-cycle gated. G2E3 is an H3K14ub-specific, pericentromeric-heterochromatin-localised E3 ligase; G2E3-catalysed H3K14 mono-ubiquitination potentiates H3K9me3 by SUV39H and is specifically required for SUV39H compartmentalisation and H3K9me3 in pericentromeric heterochromatin; G2E3 is highly expressed in G2/M and associates with mitotic chromosomes in an RNA-dependent manner; the SUV39H chromodomain reads dual H3K9me3 and H3K14ub and SUV39H associates with pericentromeric heterochromatin primarily through its H3K14ub-binding activity; and loss of G2E3 severely impairs pericentromeric heterochromatin organisation and causes aberrant accumulation of SUV39H and H3K9me3 in numerous EUCHROMATIN regions with widespread transcriptional repression.

    A conserved H3K14ub-driven H3K9me3 for chromatin compartmentalization. · Huang Y, Sun Y, Qi H, Jiang Q, et al. · Nature 2025
    PMID 41094145DOI
    ▸What this evidence cannot show

    Abstract level; cell systems not named in the abstract. The abstract writes 'SUV39H' throughout, so most statements cannot be assigned to SUV39H1 versus SUV39H2 - and this entry does not assign them. The compartment studied is pericentromeric heterochromatin, which is not the chromatin state of a transcribed CTCF loop anchor.

    ▸Evidence that argues against this (2)

    • The euchromatic-spillover result is a direct argument against any strategy that manipulates this machinery for a locus-specific effect: losing one upstream ligase moves SUV39H and H3K9me3 into numerous euchromatic regions with widespread repression. A perturbation intended to change the mark at one CTCF element is not expected to stay there.
    • It also offers an alternative explanation of the ASB7 circuit's phenotype. If SUV39H compartmentalisation is gated by a G2/M-expressed ligase reading H3K14ub, then a mitotic H3K9me3 change following ASB7 or CDK1 perturbation could run through G2E3 rather than through SUV39H1 degradation, and the two 2025 papers do not cite each other's mechanism.
13. E13established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    SUV39H1 is not a dependency in the CRISPR panel. Flattening every tissue block of the DepMap essentiality payload gives 1,258 screens with a gene effect, mean -0.0575, median -0.0454, minimum -0.8362, with 0.72% of lines below -0.5 and none below -1.0; in the 147 screens from the hematopoietic and lymphoid tissue blocks the mean is -0.109 with 6.1% below -0.5. For contrast in the same call and the same data version, SETDB1 gives mean -0.529 with 50.4% of lines below -0.5 (blood mean -0.649, 63.3% below -0.5) and MEN1 gives mean -0.362 with 28.9% below -0.5 (blood mean -0.583).

    Open Targets Platform GraphQL API, target.depMapEssentiality with all tissue blocks flattened, plus meta.dataVersion · Open Targets Platform; Broad Institute DepMap · Open Targets Platform 2026
    ▸What this evidence cannot show

    Rule 83: the payload carries no DepMap release identifier, only the Open Targets data version (year 26, month 06), and a fetch date is not a release. Rule 84: no median-split proportion is reported here and none should be derived from these numbers. A pan-panel mean is the wrong statistic for comparing a selective dependency with a broad one, which is why the blood split and the absolute-threshold fractions are given. The panel contains no infant KMT2A::AFF1 line, and the guard plus the POLR2A zero-screen control were both run in the same call - POLR2A returns 0 blocks and 0 screens while its approvedSymbol readback passes, so an empty row would have looked like a flat dependency.

    ▸Evidence that argues against this (2)

    • A flat dependency is exactly what a tumour suppressor produces, so this measurement cannot distinguish 'SUV39H1 does nothing in these cells' from 'SUV39H1 restrains them'. Reading it as evidence of dispensability would invert [E2]. Nothing in a loss-of-viability screen can detect a gene whose loss accelerates disease.
    • SUV39H1 is X-linked, and a CRISPR screen in a panel of aneuploid lines with variable X copy number and variable X-inactivation is a setting where a single-copy target's knockout efficiency differs systematically from an autosomal gene's. Nothing in the payload addresses that, so the comparison with the autosomal SETDB1 is not like for like.
14. E14moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Chaetocin, the compound every published 'SUV39H1 inhibition' phenotype rests on, is a nonspecific inhibitor of histone lysine methyltransferases.

    Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases. · Cherblanc FL, Chapman KL, Brown R, Fuchter MJ · Nature Chemical Biology 2013
    PMID 23416387DOI
    ▸What this evidence cannot show

    TITLE-LEVEL ONLY. This is a correspondence item and efetch returns NO abstract text for it, so nothing beyond the title is asserted here - specifically, no potency number, no assay and no list of which methyltransferases were tested. The original authors published a reply in the same issue (PMID 23416388), which also has no abstract, so the exchange is on record as unresolved at the level this project can read. Anyone building on this should read both PDFs.

    ▸Evidence that argues against this (1)

    • The reply exists and this entry has not read it. PMID 23416388, by the group that originally characterised chaetocin as a SUV39H1 inhibitor, disputes the claim; recording only the challenge would misrepresent the state of the argument. The honest position is that chaetocin's selectivity is contested in print and that no experiment in this graph can adjudicate it.
15. E15strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Chaetocin's selective anticancer effect has a documented alternative mechanism that is not SUV39H1: it is a competitive and selective substrate of thioredoxin reductase-1 with a Km of 4.6 +/- 0.6 uM against the native substrate thioredoxin's 104.7 +/- 26 uM, thereby attenuating reduction of thioredoxin at achieved intracellular concentrations; over-expression of thioredoxin in HeLa cells conferred resistance to chaetocin-induced but NOT doxorubicin-induced cytotoxicity; and the authors attribute chaetocin's selective anticancer effects to ROS imposition via TrxR1 inhibition.

    The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase. · Tibodeau JD, Benson LM, Isham CR, Owen WG, et al. · Antioxidants & Redox Signaling 2009
    PMID 18999987DOI
    ▸What this evidence cannot show

    Abstract level; the cellular arm is HeLa. This establishes that a non-SUV39H1 mechanism is sufficient to explain chaetocin's selective cytotoxicity, not that chaetocin has no methyltransferase activity - the two are compatible.

    ▸Evidence that argues against this (2)

    • It does not exonerate SUV39H1 as a target: the AML differentiation result at NON-cytotoxic chaetocin concentrations (PMID 25978433), which also reported reduced SUV39H1 protein and reduced H3K9me3 on long incubation, is not obviously explained by a ROS mechanism that manifests as cytotoxicity. A redox mechanism for the killing and a chromatin mechanism for the differentiation can both be true.
    • The thioredoxin-resistance control was run against doxorubicin and not against a second methyltransferase inhibitor, so the experiment separates chaetocin from an anthracycline rather than separating its redox activity from its chromatin activity.
16. E16moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The one head-to-head of SUV39H1 and G9a pharmacology in AML found no synergy between them, and found the two inhibitors to be different in kind. The SUV39H1 inhibitor chaetocin and the G9a inhibitor UNC0638 both caused cell death in AML cells at high concentrations, but only chaetocin induced CD11b expression and differentiation at non-cytotoxic concentration; HL-60 and KG-1a were more sensitive than U937; long-term chaetocin downregulated SUV39H1 and reduced H3K9 trimethylation in HL-60 and KG-1a; chaetocin synergised with SAHA and with a BET bromodomain inhibitor; and NO synergism was found by combining chaetocin with UNC0638. Differentiation and combined cytotoxicity were reproduced in primary AML patient cells.

    The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells. · Lai YS, Chen JY, Tsai HJ, Chen TY, et al. · Blood Cancer Journal 2015
    PMID 25978433DOI
    ▸What this evidence cannot show

    Abstract level. The lines are HL-60, KG-1a and U937 - myeloid, none KMT2A::AFF1; KG-1a and U937 both appear in the founding rearrangement paper's cytogenetic arm, which is a coincidence of cell choice and not a connection. Chaetocin is used as though it were a SUV39H1 inhibitor, which [E14] and [E15] dispute, so this paper's attribution of its own phenotype is exactly what is in question. 'No synergism' is a negative from a fixed-concentration combination and is not a formal isobologram claim at abstract level.

    ▸Evidence that argues against this (2)

    • The absence of chaetocin/UNC0638 synergy is a weak negative that this graph should not lean on either. Two drugs acting on the same pathway are not expected to synergise, so a null here is equally consistent with both hitting H3K9 methylation and with chaetocin not hitting it at all - the experiment cannot separate those, and it is the only published interaction test between a SUV39H1 tool and a G9a tool in any leukaemia.
    • UNC0638 is the predecessor of UNC0642, the compound this graph's rearrangement mechanism proposes prophylactically. This paper reports it killing AML cells at high concentration, which is a pharmacological fact about a leukaemic blast that the prophylaxis argument - framed entirely around a pre-leukaemic locus event - does not address.

• ← co-occurs withBRCA1 (P38398, 1,863 aa) - named in 19 entries of this graph and never written: the HR mediator that CTCF and the H3K9 machinery are now reported to license at a break, and the only cascade member with a human therapy-related-leukaemia signal after topoisomerase II therapy

  SUV39H1 is one of the repressive chromatin proteins whose CTCF-dependent enrichment precedes BRCA1/BARD1 accumulation at breaks

• regulates →H3K9me3 - measured in KMT2A::AFF1 cells, in a supplementary figure, and it rises GENERALLY where H3K27ac falls SPECIFICALLY in the same experiment

  writes H3K9me3 - the canonical constitutive-heterochromatin H3K9 trimethyltransferase

• regulates →KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3)

  tumour suppressor in mouse MLL-AF9 AML: Suv39h1 over-expression lengthens latency and reduces LSC frequency, knockdown accelerates

• ← bindsMEN1 / menin — the adaptor the fusion cannot work without

  menin SvID (aa 360-445), a surface distinct from the MLL-binding central cavity; patient mutants D418N and W436R lose binding

• ← recruitsCDC73 / parafibromin — the PAF1C subunit that was genetically tested, and a second tumour suppressor required by the fusion

  parafibromin aa 128-227 recruits SUV39H1 to the cyclin D1 promoter for H3K9 methylation; SHP2 dephosphorylation flips it to beta-catenin

• ← recruitsCTCF - named in the id of an existing entry in this graph and having no entry of its own, and the protein whose binding sites break preferentially in KMT2A-rearranged patients

  CTCF recruits HP1-gamma, KAP1, SUV39H1, SETDB1 and KDM5A to double-strand breaks; CTCF depletion abrogates the enrichment (U2OS/HEK293T)

• ← recruitsTRIM28 / KAP1 / TIF1beta (Q13263) - the KRAB-ZFP corepressor scaffold in the pan-MLL-fusion core, with the weakest index-fusion p-value but a leukaemic role in another fusion family

  KAP1/HP1/SUV39H1 complex loads at breaks and spreads H3K9me3 tens of kb; ATM phosphorylation of KAP1 releases it

• ← inhibitsASB7 (Q9H672) - the brake on H3K9me3's own positive feedback loop, released by CDK1 in mitosis, and it reached this graph as the flattest dependency in the read queue

  CUL5-ASB7 ubiquitinates SUV39H1 for degradation; HP1 recruits the ligase and CDK1 phosphorylation of ASB7 releases the brake in mitosis

• related to →SETDB1 (Q15047, KMT1E/ESET) - the second H3K9me3 writer: it represses the fusion's own targets via the PAF1 complex, it is required in fetal liver HSPCs and in leukaemic stem cells, and it is a broad dependency in half the CRISPR panel - three published directions that do not agree

  the two H3K9me3 writers, separable on compartment (pericentromeric/laminar/nucleolar versus non-pericentromeric and nucleolus-excluded) and on dependency (flat versus broad), and neither ever measured at the KMT2A locus

• related to →Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor

  bite-back: menin delivers SUV39H1 to chromatin, and removing menin from a promoter removes SUV39H1 from it - so a menin inhibitor is predicted to lower menin-delivered H3K9me3, which has never been measured under any menin inhibitor

• related to →The H3K9me1/2-CTCF brake: a KDM3B-G9a balance keeps the KMT2A breakpoint cluster region methyl-poor and CTCF-bound, and losing either end makes the locus amplify and rearrange - in epithelium, in primary cord-blood progenitors and in mice

  the enzyme whose product that mechanism argues about, with the writer's only documented route to a CTCF-bound element being CTCF itself

• ← recruitsCBX5 / HP1-alpha (P45973, 191 aa) - the H3K9me3 reader that recruits the writer, the writer's destroyer and the second writer; and the one member of that circuit with a published pro-leukaemic role, as part of an MLL leukaemia stem-cell programme that immortalises myeloid progenitors WITHOUT Hoxa or Meis

  HP1 recognises pre-existing H3K9me3 and recruits SUV39H1 to methylate adjacent new histones - the self-templating loop

• ← related toNo H3K9me3 writer and no H3K9me3 reader has ever been localised at the KMT2A locus IN THE PUBLISHED LITERATURE, in any cell type: 20 queries, 5 alias spellings, 0 on-topic records - and CORRECTED 2026-09-22: the SUV39H1 half is no longer unanswerable from archives. ENCODE still holds zero SUV39H1 experiments (verified by three routes with controls), but GEO holds two deposits, and Q114 read both at this locus and found the writer ABSENT

  the writer whose absence at this locus is total: 0 literature reports AND 0 ENCODE ChIP-seq experiments in any cell type

• ← related toThe GEO sweep that q110 named as free and did not run: SUV39H1 chromatin occupancy HAS been measured in two human cell types, six samples, hg38 bigWigs already deposited - so the writer half of the H3K9me3 absence is measured-not-analysed, not never-measured

  first chromatin-occupancy datasets for this protein recorded in this graph: GSE225028 (CUT&RUN, hg38 bigWig, two DIPG lines) and GSE139196 (ChIP-Seq, MCF-7)

• ← related toGSE225028: SUV39H1 and H3K9me3 CUT&RUN in SU-DIPG13 and SU-DIPG36 - the only published human SUV39H1 occupancy map deposited as a readable hg38 bigWig, and the enzyme and its own mark were profiled in the same cells

  the only published human SUV39H1 occupancy map with its own mark profiled in the same nuclei

• ← related toGSE139196: SUV39H1 ChIP-Seq in MCF-7 with and without 40 minutes of estradiol - a ligand-inducible SUV39H1 occupancy experiment, filed under the retired symbol KMT1A in its own sample titles

  four ChIP-Seq samples plus and minus 40 min estradiol, filed under the alias KMT1A

• ← related toThree archives, one answer: SUV39H1 has no ENCODE target record under any label (three routes, all empty), ChIP-Atlas's entire hg38 SUV39H1 holding IS the four GSE139196 MCF-7 samples re-indexed, and KMT2A is not among the 26 genes ChIP-Atlas calls SUV39H1 targets

  complete archive census of human SUV39H1 occupancy data, 2026-09-22

• ← testsThe deposit this graph filed as 'four SUV39H1 ChIP-seqs' is actually 77 samples in MCF-7 carrying the ENTIRE H3K9 axis in one cell type and one pipeline - writer SUV39H1, writer G9a/EHMT2, reader HP1-alpha/CBX5 (wild-type AND two phospho-mutants), co-repressor KAP1/TRIM28, erasers KDM4B and KDM4C, the mark H3K9me3, and an shKDM4B+shKDM4C eraser-knockdown arm

  the four SUV39H1 (KMT1A) samples, the only condition-contrasted SUV39H1 occupancy data in existence

• ← testsRead at last, against a pre-registered class-matched null: in SU-DIPG13 and SU-DIPG36 the SUV39H1 CUT&RUN mean at the KMT2A exon-11 CTCF anchor is 0.0000 and 1.6660 - the first an EXPLICIT zero record, not missing data - and no one of the seven KMT2A intervals in either line exceeds 1.21x the genome-wide random-tile mean. The pre-registered NEGATIVE prior held.

  first reading of a human SUV39H1 occupancy track at the KMT2A locus

• ← related toThe rarest thing in the deposit, measured: across 59,821 CTCF anchors in the SAME nuclei, SUV39H1 occupancy and H3K9me3 correlate at Spearman 0.148 and 0.078 - and a quarter to two-fifths of the enzyme's own strongest sites carry no more of its mark than the median anchor

  SUV39H1 is absent from 55.9-63.3% of CTCF anchors and off its own mark at a quarter to two-fifths of its strongest sites

• ← testsThe one experiment that would close the SUV39H1 arm of this graph's H3K9 argument: CST #8729S CUT&RUN in a CD34+ progenitor and in SEM or RS4;11, with an IgG arm and a SUV39H1-degron arm that neither existing deposit has - because after this cycle the enzyme has been measured in exactly two human cell types and neither is a blood cell

  the occupancy measurement that does not exist in any blood cell

• ← related toBounded with every archive and every route named: after both public SUV39H1 deposits were read this cycle, there is still NO SUV39H1 occupancy measurement in any haematopoietic cell, any KMT2A-rearranged cell, or any damage state - in ENCODE (three routes, zero), ChIP-Atlas (one deposit, MCF-7 only) or GEO (two deposits, glioma and breast)

  the lineage gap that survives after both deposits were read

• ← related toThe H3K9me3 this graph argues about at the KMT2A exon-11 anchor is not deposited by SUV39H1: in SU-DIPG13 the mark sits at the 57.8th percentile of class-matched CTCF anchors while the writer reads an EXPLICIT ZERO in the same nuclei, and genome-wide the two barely track each other (Spearman 0.148, 0.078)

  assigns this enzyme no role at the exon-11 anchor

• ← testsThe MCF-7 arm, and the clause that saved it: SUV39H1 at the exon-11 anchor reaches the 96.3rd percentile of 56,171 same-cell-type CTCF anchors in one replicate - but all six non-anchor KMT2A intervals are elevated too (medians 73-87), so the pre-registered FIRES clause does not fire, the verdict is NEITHER, and four replicates of one antibody in one cell line span 51.8 to 96.3 at the same 147 bp

  SUV39H1 occupancy at seven KMT2A intervals in MCF-7, four replicates

• ← related toEstradiol does not redistribute SUV39H1 - because the replicates do not agree well enough to see it: over 56,171 CTCF anchors the ACROSS-condition Spearman (0.358) is HIGHER than the within-condition replicate correlations (0.326 for -E2, 0.207 for +E2), and the same 147 bp anchor reads 51.8, 69.1, 90.8 and 96.3 in the four samples

  the only replicate-concordance estimate for any SUV39H1 occupancy data: rho 0.21-0.33

• supports →BRCA1 (P38398, 1,863 aa) - named in 19 entries of this graph and never written: the HR mediator that CTCF and the H3K9 machinery are now reported to license at a break, and the only cascade member with a human therapy-related-leukaemia signal after topoisomerase II therapy

  H3K9me3 written at the break is the licence for early BRCA1/BARD1 loading

• ← bindsThe SvID, menin 360-445: a truncation boundary the field reads as a domain, whose functional residues D418 and W436 are 10-20 A from every menin drug - but whose first ten residues ARE the drug pocket

  patient mutants D418N and W436R lose binding; A411P and L413P do not

• ← refutesADJUDICATION: the SvID and the gamma-H2A.X motif are OVERLAPPING BUT NOT THE SAME SURFACE - and the premise that made the question urgent, that the SvID is distinct from the MLL cavity, is FALSE at the SvID's own boundary

  refutes the reason given in that entry's menin-connection section - the SvID is NOT a different surface from the MLL cavity at residues 360-371