PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check

This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.

• PRMT7 loss of function causes a germline human developmental syndrome - SBIDDS, with short stature, brachydactyly, impaired intellectual development and seizures. That is the essential-function toxicity axis for any PRMT7 inhibitor, and it is a developmental phenotype, which is the worst possible class for a drug intended for infants. This project's index disease is infant leukaemia.
• The probe's own paper shows PRMT7 inhibition DECREASES tolerance for proteostasis perturbation, including heat shock and proteasome inhibitors (PMID 32409666). Any combination with a proteasome inhibitor, or any regimen imposing proteotoxic stress, carries an on-target sensitisation that is not selective for leukaemic cells.
• The CML result is a self-renewal phenotype with a claimed sparing of normal haematopoiesis, and it is metabolic rather than epigenetic - glycine decarboxylase and methylglyoxal (PMID 35508169). So the most encouraging PRMT7 result in leukaemia does NOT run through the histone mark this beat cares about, and an inhibitor developed on the metabolic rationale would not be expected to have a chromatin pharmacodynamic. Attributing efficacy to H4R3me2s would misdirect the biomarker.
• If PRMT7's mark represses a KMT2-family enzyme, then inhibiting PRMT7 RELEASES that enzyme - and in a HOXA-driven leukaemia releasing a KMT2-family H3K4 methyltransferase at HOXA/HOXB is plausibly pro-leukaemic. PRMT7 knockdown increases KMT2D-catalysed H3K4me3 at exactly those genes (PMID 23249737). The direction of benefit is not established and could be inverted.
• PRMT7 is not a DepMap dependency (mean -0.1513 over 1,258 lines, 1.67% depleted), so no cell-line screen will support prioritising it and any in vitro proliferation experiment is likely to read as a negative. The assays that show a phenotype are primary-cell self-renewal and in vivo, which are the expensive ones - a real programme cost, not a scientific objection.

1. Is PRMT7 type II or type III IN CELLS? Every symmetric-dimethyl mechanism attributed to it depends on the answer, and the discriminating experiment is a stable-isotope methyl-labelling and isomer-resolving mass-spectrometry read of H4R3 states in a PRMT7 knockout versus a PRMT5 knockout in the same cell. A type III result would not kill the mechanisms - it would place PRMT7 one step upstream of them, supplying monomethyl substrate.
2. Does PRMT7 loss relieve a KMT2-family blockade in a KMT2A-rearranged cell? The KMT2D result (PMID 23249737) is the right direction on the right genes (HOXA/HOXB) in the wrong cell. A PRMT7 knockout or SGC3027 exposure in SEM or MV4;11, read out as H3K4me3 at HOXA9/MEIS1 plus H4R3 states by mass spectrometry, is one experiment and has never been done - PRMT7[tiab] AND KMT2A[tiab] = 0.
3. Why do PRMT6 and PRMT7 both land on RUNX1 target genes through different marks in different lineages? PRMT6/H3R2me2a deregulates RUNX1 targets (PMID 22777353, carried in gene-prmt6 and gene-runx1); PRMT7 deregulates RUNX1 targets in T-ALL (PMID 35565298). Two points and no connecting mechanism, but RUNX1 has an entry here and the coincidence is in the haematopoietic compartment this project cares about.
4. Does the degenerate C-terminal PRMT domain do anything? PRMT7 is the only family member in this graph with two tandem methyltransferase modules, there is no structure of the human protein at all, and the function of the second module is unresolved - which also means no structure-guided argument about PRMT7's substrate selection can be made here.

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

   UniProt Q9NVM4 (ANM7_HUMAN, primary gene PRMT7, synonym KIAA1933, 692 aa, two SAM-dependent MTase PRMT-type domains at 14-345 and 358-684) records that PRMT7 can both catalyze the formation of omega-N monomethylarginine and symmetrical dimethylarginine with a preference for MMA, that it specifically mediates symmetrical dimethylation of the small nuclear ribonucleoproteins SNRPD1 and SNRPD3 as required for snRNP core particle assembly, that it specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s, and that it is recruited by CTCFL at the H19 imprinted control region where it methylates histone H4 to form H4R3me2s; the annotated CATALYTIC ACTIVITY reaction is the monomethyl one; subcellular location is Cytoplasm/cytosol and Nucleus, both ECO:0000269:PubMed:15494416; loss-of-function causes SBIDDS (short stature, brachydactyly, impaired intellectual development and seizures), autosomal recessive; H3R2 is not named anywhere in the FUNCTION block.

   UniProtKB Q9NVM4 (ANM7_HUMAN) - protein arginine methyltransferase 7; FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISEASE and domain feature table, read back 2026-09-22 · UniProt 2026
   ▸What this evidence cannot show

   A curated annotation, not a measurement; accession fetched live rather than recalled. The record is internally tense: it asserts sDMA capability while annotating a monomethyl-only reaction. Several histone statements are hedged ('possibly leading to recruit DNA methyltransferases') or flagged as unclear in vivo ('also able to mediate the arginine methylation of histone H2A and myelin basic protein in vitro; the relevance of such results is however unclear in vivo'). RULE-91 NOTE: the ONLY experimental citation behind both subcellular-location values is PubMed:15494416, the 2005 founding paper whose central enzymological conclusion - that PRMT7 synthesises symmetric dimethylarginine - is the disputed one.

   ▸Evidence that argues against this (1)

   • The type II assignment the database carries is contradicted by a dedicated product-specificity study which found only monomethylarginine under every condition tested, including on recombinant human histones. So the curated 'can form sDMA' is itself an unresolved claim, and any mechanism built on PRMT7 as a direct symmetric-dimethyl writer inherits that dispute. Zurita-Lopez CI et al. 2012
2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   Full-length human PRMT7 expressed as a GST fusion with robust activity produced only omega-N-monomethylarginine on a variety of arginine-containing synthetic peptides and protein substrates including GST-GAR (the fibrillarin N-terminal domain), myelin basic protein and recombinant human histones H2A, H2B, H3 and H4, regardless of incubation time, reaction volume or substrate concentration, while control mammalian GST-PRMT1 and Myc-PRMT5 dimethylated their peptides to the expected asymmetric and symmetric products - so PRMT7 is a type III human methyltransferase capable of forming only monomethylarginine under the conditions tested.

   Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming omega-NG-monomethylated arginine residues. · Zurita-Lopez CI, Sandberg T, Kelly R, Clarke SG · J Biol Chem 2012
   PMID 22241471DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. In vitro, with a bacterially expressed GST fusion; the authors note a previous study characterised bacterially and mammalian-expressed PRMT7 fusions as type II/type I and qualify their own conclusion with 'under the conditions tested'. An in vitro negative on recombinant histone components does not exclude symmetric dimethylation of a nucleosomal substrate in a cell with cofactors, partners or allosteric regulation present.

   ▸Evidence that argues against this (1)

   • Two independent cellular experiments report symmetric dimethyl phenotypes for PRMT7: a knockdown that raises H4R3me2s at KMT2D targets where PRMT5 does not, and a B-cell conditional knockout in which PRMT7 recruits both H4R3me1 and symmetric H4R3me2 to the Bcl6 promoter. Either PRMT7 makes sDMA in cells under conditions not reproduced in vitro, or it primes another enzyme by supplying monomethylarginine - and a type III enzyme feeding a type II one would produce exactly the observed pattern. Ying Z et al. 2015
3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   The binding strength of the tandem plant homeodomain PHD(4-6) of MLL4 - the enzyme the paper also calls MLL2 and ALR, i.e. KMT2D - is inhibited by H4R3 symmetric dimethylation, and PHD(4-6) is required for MLL4's nucleosomal methyltransferase activity; PRMT7, but not PRMT5, represses MLL4 target genes by upregulating H4R3me2s levels and antagonises MLL4-mediated differentiation; PRMT7 knockdown increases MLL4-catalysed H3K4me3 levels; and during differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes including many HOXA and HOXB genes.

   Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. · Dhar SS, Lee SH, Kan PY, Voigt P, et al. · Genes Dev 2012
   PMID 23249737DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read; no residue numbers asserted for PHD(4-6) because none were fetched from a sequence. NOMENCLATURE: the paper's 'MLL4' is KMT2D, settled by the aliases MLL2 and ALR and by the Kabuki-syndrome attribution in its own abstract, and NOT KMT2B, whose MLL4 alias travels with WBP7. System is NT2/D1 embryonal carcinoma differentiation - not haematopoietic, not leukaemic, and the enzyme is KMT2D not KMT2A. The PRMT7 arm is a knockdown, so an indirect route through PRMT7's non-histone substrates is not excluded.

   ▸Evidence that argues against this (1)

   • If PRMT7 is a type III monomethyl-only enzyme as a dedicated product-specificity study concluded, PRMT7 cannot be the direct writer of the H4R3me2s this mechanism depends on, and the knockdown phenotype would be indirect - most plausibly through loss of the monomethyl substrate a type II enzyme needs. The mechanism could hold with PRMT7 one step removed from the mark. Zurita-Lopez CI et al. 2012
4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In mice with a B-cell-specific knockout of PRMT7, loss of PRMT7 led to decreased mature marginal-zone B cells, increased follicular B cells and promoted germinal-centre formation after immunisation, with low secreted IgG1 and IgA and abnormal expression of the germinal-centre genes Bcl6, Prdm1 and Irf4; overexpression of PRMT7 in the B-lymphoma-derived Raji and A20 lines validated that PRMT7 negatively regulates Bcl6 expression, and chromatin immunoprecipitation-PCR showed PRMT7 recruits H4R3me1 and symmetric H4R3me2 to the Bcl6 promoter.

   Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription. · Ying Z, Mei M, Zhang P, Liu C, et al. · J Immunol 2015
   PMID 26179907DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. Murine B-lineage in vivo plus two B-lymphoma cell lines - genuinely B-lineage, which is rare for this enzyme, but mature B-cell and germinal-centre biology, NOT a pro-B or fetal-liver progenitor and NOT a KMT2A-rearranged cell. The ChIP-PCR is antibody-based at a single promoter and the isomer specificity of the reagents is not addressed, which for H4R3me1 versus symmetric H4R3me2 is the constraint that matters. 'Recruits' is the abstract's own word and conflates PRMT7 occupancy with mark deposition.

   ▸Evidence that argues against this (1)

   • Because the same experiment reports both H4R3me1 and symmetric H4R3me2 at the promoter, and because a dedicated in vitro study says PRMT7 makes only monomethylarginine, the symmetric species could be deposited by a different enzyme acting on PRMT7-supplied monomethyl substrate. The result establishes PRMT7's requirement at the locus, not that PRMT7 is the symmetric writer. Zurita-Lopez CI et al. 2012
5. E5weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper

   Histone H3 arginine 2 is symmetrically dimethylated by PRMT5 and PRMT7 to give H3R2me2s, present in euchromatic regions, a mark that excludes RBBP7 and whose effect on WDR5 binding distinguishes it from H3R2me2a.

   Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance. · Migliori V, Müller J, Phalke S, Low D, et al. · Nat Struct Mol Biol 2012
   PMID 22231400DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. CONFIDENCE IS DELIBERATELY WEAK for the PRMT7 attribution specifically - it is a single clause naming PRMT7 alongside PRMT5 in a paper whose focus and downstream analyses are PRMT5-centred, it is not carried by UniProt, and it is contradicted in principle by the same-year type III study. 'H3R2me2s'[tiab] AND PRMT7[tiab] returns only 2 records, one of which is this paper, so no independent replication of the PRMT7 half was found. The claim about WDR5 binding was itself revised in 2020 (see mark-h3r2me2s).

   ▸Evidence that argues against this (1)

   • UniProt's FUNCTION block for PRMT7 does not name H3R2 at all and assigns PRMT7's specific histone mark as H4R3me2s. Combined with the type III enzymology study and the absence of independent replication, this graph records PRMT7 as a weak H3R2me2s writer, and the dispatch brief's unqualified description of it as 'a second H3R2me2s writer' is not supported at that strength. UniProt 2026
6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   Genetic loss of Prmt7 and a small-molecule specific inhibitor of PRMT7 each delayed leukaemia development and impaired self-renewal of leukaemia stem cells in a CML mouse model and in primary human CML CD34+ cells, without affecting normal haematopoiesis; mechanistically, PRMT7 loss reduced expression of glycine decarboxylase, reprogramming glycine metabolism to generate methylglyoxal, which is detrimental to leukaemia stem cells.

   Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML. · Liu C, Zou W, Nie D, Li S, et al. · Cell Metab 2022
   PMID 35508169DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. CHRONIC MYELOID LEUKAEMIA, a BCR::ABL1 disease - not a KMT2A rearrangement and not lymphoid. 'Without affecting normal hematopoiesis' is a strong therapeutic-window claim made in an abstract and was not verified against the figures. The mechanism given is metabolic rather than chromatin, so this paper is a PRMT7 dependency result and NOT evidence about any histone arginine mark; the abstract's closing phrase 'links histone arginine methylation with glycine metabolism' is not supported by anything described in the abstract itself.

   ▸Evidence that argues against this (1)

   • PRMT7 is not a DepMap dependency in cell-line screens - mean gene effect -0.1513 across 1,258 screened lines with only 1.67% of lines depleted below -0.5, and a lymphoid-tissue mean of -0.1039 over 97 lines. A stem-cell self-renewal requirement in a mouse model and in primary CD34+ cells is not contradicted by that, because LSC self-renewal is not what a proliferation screen measures, but it does mean no cell line should be expected to depend on PRMT7 and an in vitro cell-line experiment is the wrong assay. Open Targets Platform / DepMap 2026
7. E7moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   Across haematological malignancies, PRMT7 mRNA is high in T-cell acute lymphoblastic leukaemia and particularly in the mature subtypes of T-ALL; CRISPR-Cas9 deletion of PRMT7 reduced colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with RNA and DNA processing and with T-ALL pathogenesis, among them RUNX1, whose target gene expression was consequently deregulated.

   Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia. · Oksa L, Mäkinen A, Nikkilä A, Hyvärinen N, et al. · Cancers (Basel) 2022
   PMID 35565298DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. T-lineage ALL, not B-lineage and not KMT2A-rearranged; the disease this project is about is infant B-ALL. The measured methylation change is arginine MONOmethylation, consistent with the type III reading of the enzyme and NOT a symmetric dimethyl result. Colony formation is a single functional readout. The RUNX1 link is 'among them' in a proteomic list plus a downstream expression change, not a demonstrated direct methylation event at a mapped residue.

   ▸Evidence that argues against this (1)

   • That the measured consequence is monomethylation rather than symmetric dimethylation cuts against the histone-symmetric-dimethyl model of PRMT7 in a leukaemic cell, and points the mechanism at non-histone substrates in RNA and DNA processing complexes. A reader should not transfer this T-ALL dependency onto the H4R3me2s/KMT2D mechanism - they may be two different PRMT7 biologies. Szewczyk MM et al. 2020
8. E8strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   SGC3027 is a potent, selective and cell-active chemical probe for PRMT7: a cell-permeable prodrug converted in cells to SGC8158, a potent SAM-competitive PRMT7 inhibitor; inhibition or knockout of cellular PRMT7 drastically reduces arginine monomethylation of HSP70-family stress-associated proteins, PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound open conformation of HSP70, and SGC3027 decreases tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors.

   Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response. · Szewczyk MM, Ishikawa Y, Organ S, Sakai N, et al. · Nat Commun 2020
   PMID 32409666DOI
   ▸What this evidence cannot show

   Abstract read from the eutils record 2026-09-22; full text not read. A chemical probe, NOT a clinical agent - no PRMT7-selective compound has entered a clinical trial as far as this beat established, and no trial registry search for PRMT7 was run. The cellular readout that validates target engagement is arginine MONOmethylation of HSP70, not any histone mark, so this probe's published pharmacodynamic does not report on H4R3me2s or H3R2me2s at all. The proteostasis phenotype is a general cell-biological effect and not leukaemia-specific.

   ▸Evidence that argues against this (1)

   • A probe whose validated cellular pharmacodynamic is HSP70 monomethylation cannot be used to attribute a phenotype to a histone arginine mark without an independent chromatin measurement, and PRMT7 inhibition sensitises cells to proteasome inhibitors and heat shock - an on-target liability that would confound any combination study in a disease already treated with proteostasis-stressing agents. Liu C et al. 2022
9. E9strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   PRMT7 (ENSG00000132600) is NOT flagged essential in DepMap CRISPR (Chronos): mean gene effect -0.1513 across 1,258 screened cell lines with 1.67% of lines depleted below -0.5, and a lymphoid-tissue mean of -0.1039 over 97 lines; HGNC:25557 assigns PRMT7 to 16q22.1 with the single UniProt id Q9NVM4 and Ensembl gene ENSG00000132600; RCSB returns ZERO structures for Q9NVM4 and UniProt carries no PDB cross-reference, so there is no experimental structure of human PRMT7.

   DepMap CRISPR (Chronos) gene-effect distribution for PRMT7 via Open Targets Platform GraphQL; HGNC REST record for PRMT7; RCSB Search API accession query for Q9NVM4 - all fetched 2026-09-22 · Open Targets Platform / DepMap / HGNC / RCSB PDB 2026
   ▸What this evidence cannot show

   RULE 83: the API does NOT state a DepMap release, so the release is unverified and only the fetch date is recorded; DepMap ships quarterly and screens each gene in a gene-specific number of lines, so 1,258 is PRMT7's own screen count and not a corpus denominator. The RCSB query returned HTTP 204 (no content) for the accession-index search, which this beat reads as zero entries; that is a negative from one query form, and a structure deposited under a mouse or trypanosomal PRMT7 accession would not appear. No KMT2A-selectivity join was performed for PRMT7 because the mean effects are within 0.16 Chronos units of zero and any selectivity rank would be a ranking of noise.

   ▸Evidence that argues against this (1)

   • A cell-line proliferation screen is the wrong assay for a stem-cell self-renewal dependency. Prmt7 loss impairs leukaemia-stem-cell self-renewal in a CML mouse model and in primary human CML CD34+ cells while sparing normal haematopoiesis - a phenotype invisible to DepMap by construction. 'Not a DepMap dependency' must not be read as 'not a therapeutic target'. Liu C et al. 2022
10. E10strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    PubMed esearch 2026-09-22 with querytranslation read back and zeros re-run: PRMT7[tiab] = 172; PRMT7[tiab] AND KMT2A[tiab] = 0 (re-run 0, warninglist outputmessages ['No items found.']); AND MLL[tiab] = 1 (22231400, where 'MLL' names a WDR5-containing coactivator complex); AND menin[tiab] = 1 (32859041, a GLI arginine-methylation review); AND leukemia[tiab] = 9 (41157668, 40619015, 35675797, 35565298, 35508169, 28874563, 26179907, 23249737, 19089452); AND 'H3R2me2s'[tiab] = 2 (22231400, 33980975); AND H3R2[tiab] = 3; AND SGC3027[tiab] = 5. Operand control KMT2A[tiab] = 1652.

    PubMed esearch counts, querytranslations and warninglists for PRMT7 against KMT2A, MLL, menin, leukaemia and the H3R2 marks, run 2026-09-22 · NCBI PubMed 2026
    ▸What this evidence cannot show

    Bounds TITLES AND ABSTRACTS only. The nine leukaemia records were title-checked; 23249737 enters only through the legacy phrase 'mixed-lineage leukemia 4' in the enzyme's name and is a stem-cell differentiation paper, and 19089452 is an etoposide-cytotoxicity genome-wide association study, so counting nine as a PRMT7 leukaemia literature would overstate it - the substantive ones are 35508169, 35565298 and 26179907. No Europe PMC full-text sweep was run, so a PRMT7 measurement inside a KMT2A-fusion paper's supplementary data would be invisible here.

    ▸Evidence that argues against this (1)

    • A zero against the modern symbol is not a zero against the literature: this beat measured H4R3[tiab] AND KMT2A[tiab] = 0 while H4R3[tiab] AND MLL[tiab] = 3, so arginine-methylation work touching this gene family is old enough to use the legacy symbol. For PRMT7 both symbols were run and both are effectively empty, which is why this absence is recorded as strong rather than provisional. NCBI PubMed 2026
11. E11moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The founding characterisation of PRMT7 is titled 'PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine' - the source of the type II assignment, and the single publication behind both of UniProt's ECO:0000269 subcellular-location values for PRMT7 (Cytoplasm/cytosol and Nucleus).

    PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. · Lee JH, Cook JR, Yang ZH, Mirochnitchenko O, et al. · J Biol Chem 2005
    PMID 15494416DOI
    ▸What this evidence cannot show

    Title and bibliographic record fetched from the eutils record 2026-09-22; the ABSTRACT WAS NOT READ for this item and no experimental detail from it is asserted here - it is cited to identify the source of the type II assignment and of UniProt's localisation evidence code, which is a bibliographic claim. Whether the paper contains a localisation experiment at all was NOT verified, which is precisely the rule-91 gap being flagged: an ECO:0000269 code means a curator saw an experiment somewhere in the paper, not that the paper is about subcellular localisation.

    ▸Evidence that argues against this (1)

    • This paper's central conclusion - that PRMT7 synthesises symmetric dimethylarginine - was directly contradicted seven years later by a dedicated product-specificity study. Since the same paper is UniProt's sole experimental support for PRMT7's subcellular location, a reader should note that the localisation annotation and the disputed enzymology rest on one source and are not equally durable. Zurita-Lopez CI et al. 2012

• ← supportsFive new arginine-axis entries in one day, and not one of their genes is a selective dependency - in an instrument that recovers MEN1 at p=5e-05 and TDRD3 is not a dependency at all

  PRMT7 mean -0.1513, a non-dependency, reproducing Q103 reported figure to four decimals

• causes →H3R2me2s - the symmetric mark on the SAME residue as H3R2me2a, which permits rather than enhances WRAD access, and whose 'enhancing' half this graph inherited from the paper that was later revised

  CONTESTED writer - one sentence in PMID 22231400, contradicted by a same-year type III product-specificity study and not carried by UniProt

• causes →H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system

  the writer UniProt names specifically for this mark, and the one that raises it at KMT2D targets where PRMT5 explicitly does not

• inhibits →KMT2D (MLL2/MLL4) - the gene named in this graph's menin-resistance entry, written here for the first time

  PRMT7, but NOT PRMT5, represses KMT2D target genes by raising H4R3me2s; PRMT7 knockdown increases KMT2D-catalysed H3K4me3 at many HOXA/HOXB genes

• related to →PRMT5 - the type II arginine methyltransferase this graph has reached for sixteen times, whose mark on H3R2 RECRUITS WDR5 to chromatin

  the two symmetric-dimethyl candidates, experimentally SEPARATED: PRMT7 and not PRMT5 raises H4R3me2s at KMT2D targets, while PRMT5 is the writer at globin and in MLL-AF9

• expressed in →Pre-B cell — the stage KMT2A::AFF1 leukaemia never reaches, and why that boundary is informative

  B-cell-specific Prmt7 knockout: fewer mature marginal-zone B cells, more follicular B cells, enhanced germinal-centre formation - the only B-lineage in-vivo arginine-methyltransferase chromatin experiment in this beat

• regulates →The stem-like self-renewal state — a limited stem-cell module grafted onto a committed cell

  Prmt7 loss or inhibition impairs CML leukaemia-stem-cell self-renewal in mouse and primary human CD34+ cells, by glycine-metabolism reprogramming - NOT by a histone mark

• regulates →RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11)

  CRISPR deletion in T-ALL deregulates RUNX1 target genes - the second arginine methyltransferase to land on RUNX1, after PRMT6/H3R2me2a

• part of →Plain-English: chromatin and epigenetics — the sticky notes on the DNA, and which ones matter here

  an arginine methyltransferase whose enzyme class is still disputed between type II and type III

• ← testsMeasure H3R2 and H4R3 methylation states at KMT2A-fusion targets by isomer-resolving mass spectrometry, and test the gate by writer perturbation read out on the enzyme's product - the experiment that has never been done in any fusion

  writer of the H4R3 block, with a cell-active chemical probe (SGC3027) and a published PRMT5 negative control