PRC1.1 — the complex this graph has been leaning on, now enumerated subunit by subunit, and the enumeration changes the conclusion

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

• Every plausible PRC1.1-directed intervention points the wrong way: disrupting the complex is what confers menin-inhibitor and DOT1L-inhibitor resistance, so a PRC1.1 disruptor would antagonise the drug class this project is built around.
• The catalytic subunit RING1B is shared with all six PRC1 complexes and the adaptor SKP1 is shared with SCF, so the only chemically tractable-looking nodes are the ones whose inhibition is least selective.
• PRC1.1-deficient disease is predicted to be venetoclax-sensitive, which imports venetoclax's own resistance biology (MCL1, BCL-xL) as the next failure mode.
• If PRC1.1 loss also impairs leukaemic stem cell function, as van den Boom's KDM2B data suggest, then a PRC1.1-deficient resistant clone may be simultaneously drug-resistant and less self-renewing - a combination that would make relapse kinetics hard to predict from the in-vitro data.

1. Which PCGF flavour supplies the PRC1 catalysis that Rossi et al. showed is required for MLL-AF9 leukaemia? A PCGF-paralogue-resolved H2AK119ub map would separate PRC1.1 from canonical PRC1 and is the single most informative experiment this entry points to.
2. Does PRC1.1 do anything in KMT2A::AFF1 infant B-ALL? The complex has been studied in AML and T-ALL and never in this disease.
3. Is the BCOR/BCORL1 pair redundant in leukaemia? If so, every published single-paralogue PRC1.1 model is a partial loss of function.
4. Does the condensate description of PRC1.1 recruitment intersect the fusion's own condensate behaviour? Both are reported and nobody has looked at them together.
5. Would restoring PRC1.1 activity resensitise a resistant blast, and is there any pharmacological way to do that?

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

   PRC1.1 comprises KDM2B together with RING1B, PCGF1, and BCOR or BCORL1; it is a noncanonical PRC1 that catalyses H2AK119ub1 and binds non-methylated CpG islands through the KDM2B zinc-finger-CxxC DNA-binding domain, recruiting the complex to target gene loci.

   KDM2B in polycomb repressive complex 1.1 functions as a tumor suppressor in the initiation of T-cell leukemogenesis · Isshiki Y, Nakajima-Takagi Y, Oshima M, Aoyama K, Rizk M, Kurosawa S, Saraya A, Kondo T, Sakaida E, Nakaseko C, Yokote K, Koseki H, Iwama A · Blood Advances 3(17):2537-2549 2019
   PMID 31471323DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19. The composition sentence is the authors' framing statement rather than a result of this paper, and it omits SKP1 and RYBP, which the structural and proteomic work include. Rosters differ by purification.

   ▸Evidence that argues against this (1)

   • The four-subunit definition is demonstrably incomplete: the crystallised minimal PRC1.1 core requires SKP1 as a structural member, and the proteomic classification adds RYBP/YAF2 as the determinant of variant-PRC1 behaviour. A reader taking this roster as complete would omit the subunit that makes the complex catalytically variant. Wong SJ et al. 2016
2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

   Six major PRC1 groups each contain a distinct PCGF subunit and a RING1A/B ubiquitin ligase; association with RYBP or its homolog YAF2 prevents incorporation of canonical CBX, PHC and SCM subunits, and only RYBP stimulates RING1B activity toward H2AK119ub1; the six complexes differ in genomic localisation and only a small subset co-localises with H3K27me3.

   PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes · Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D · Molecular Cell 45(3):344-56 2012
   PMID 22325352DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. HEK293 and mouse embryonic stem cells; no leukaemia and no KMT2A fusion.

   ▸Evidence that argues against this (1)

   • Composition determined by affinity purification and mass spectrometry reports what survives a wash, not what exists. The phase-separation result for BCOR-PRC1.1 implies a condensate-associated pool whose stoichiometry would not be recovered by this method. Chen R et al. 2024
3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   Non-canonical PRC1.1, identified by mass-spectrometry proteomics, is critically important for human leukaemic stem cells: downmodulation of members such as KDM2B strongly reduces proliferation in vitro and delays or abrogates leukemogenesis in humanised xenograft models; PRC1.1 components are significantly over-expressed in primary AML CD34+ cells; and ChIP-seq shows PRC1.1 also binds a distinct set of transcriptionally active genes devoid of H3K27me3, enriched for metabolic processes.

   Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis · van den Boom V, Maat H, Geugien M, Rodriguez Lopez A, Sotoca AM, Jaques J, Brouwers-Vos AZ, Fusetti F, Groen RWJ, Yuan H, Martens ACM, Stunnenberg HG, Vellenga E, Martens JHA, Schuringa JJ · Cell Reports 14(2):332-46 2016
   PMID 26748712DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. The functional perturbation is KDM2B, a subunit shared with SCF-FBXL10, so some of the phenotype may be PRC1.1-independent. Primary AML CD34+ cells were not selected for KMT2A rearrangement.

   ▸Evidence that argues against this (1)

   • No PRC1.1-specific subunit scores as required in the genome-wide KMT2A selectivity scan, and all three score positive. Either the xenograft stem-cell phenotype is invisible to bulk proliferation assays, or the KDM2B knockdown phenotype includes a substantial SCF component. Neither possibility has been tested and the entry does not choose between them. Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
4. E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

   A minimal four-component PRC1.1 assembles from a DNA-binding KDM2B/SKP1 heterodimer plus a BCORL1/PCGF1 heterodimer; the crystal structure shows the BCORL1 PUFD domain positioning residues preceding the PCGF1 RAWUL domain to create an extended KDM2B interface unique to PCGF1-containing PRC1.1, and suggests how KDM2B might simultaneously function in PRC1.1 and in an SCF ubiquitin ligase complex.

   KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1 · Wong SJ, Gearhart MD, Taylor AB, Nanyes DR, Ha DJ, Robinson AK, Artigas JA, Lee OJ, Demeler B, Hart PJ, Bardwell VJ, Kim CA · Structure 24(10):1795-1801 2016
   PMID 27568929DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. Truncated constructs, in vitro, no RING1A/B and no nucleosome, so this is the targeting module and not a functional PRC1.1.

   ▸Evidence that argues against this (1)

   • The structure contains BCORL1, not BCOR, yet every functional leukaemia result in this entry concerns BCOR. The graph's structural picture of PRC1.1 and its functional picture are therefore built on different paralogues, and the same group later showed the two PUFD domains do not behave identically. Wong SJ et al. 2020
5. E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   RCSB PDB entry 5JH5, 'Structural Basis for the Hierarchical Assembly of the Core of PRC1.1', X-ray diffraction at 2.55 A, contains four polymer entities mapping to KDM2B (Q8NHM5, modelled 1059-1336), SKP1 (P63208, 2-163), PCGF1 (Q9BSM1, 150-255) and BCORL1 (Q5H9F3, 1668-1785), with primary citation PMID 27568929, DOI 10.1016/j.str.2016.07.011.

   RCSB PDB entry 5JH5 - Structural Basis for the Hierarchical Assembly of the Core of PRC1.1 · RCSB Protein Data Bank; entry and polymer-entity alignment records queried via data.rcsb.org 2016
   ▸What this evidence cannot show

   Entity descriptions, accessions and modelled ranges fetched from data.rcsb.org on 2026-09-19 and copied from the same fetched records, not typed from recall. Modelled ranges are RCSB-reported aligned regions and are shorter than the crystallised constructs.

   ▸Evidence that argues against this (1)

   • This is the ONLY assembled-PRC1.1 structure in the PDB, and it lacks the catalytic subunit. Every statement this project makes about PRC1.1 geometry on a nucleosome is therefore extrapolation from a targeting module, and no experiment has confirmed that the module docks the RING1B catalytic centre over H2A K119 in the way the canonical PRC1-nucleosome structures do. Gao Z et al. 2012
6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In KMT2A-rearranged AML, noncanonical menin targets bivalently co-occupied by active menin and repressive H2AK119ub are normally downregulated after menin inhibition; loss of PRC1.1 subunits such as PCGF1 or BCOR confers menin-inhibitor resistance by epigenetically reactivating these targets including MYC, MYC inhibition resensitises, and PRC1.1-deficient cells show reduced monocytic gene signatures and venetoclax susceptibility.

   Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia · Zhou X, Zhang L, Aryal S, Veasey V, Tajik A, Restelli C, Moreira S, Zhang P, Zhang Y, Hope KJ, Zhou Y, Cheng C, Bhatia R, Lu R · Blood 144(19):2018-2032 2024
   PMID 39158067DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. AML only, human and mouse; no B-lineage, no KMT2A::AFF1. Engineered loss, not clinically observed loss.

   ▸Evidence that argues against this (1)

   • The bivalency screen of Sparbier et al. reports menin inhibition paradoxically ACTIVATING bivalent genes on its own, without any PRC1.1 perturbation. If that holds in KMT2A-rearranged blasts, the requirement for PRC1.1 loss to reactivate this class of target is context-dependent rather than general, and the resistance model narrows accordingly. Sparbier CE et al. 2023
7. E7moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   A Perturb-seq map of KMT2A-rearranged AML reports that disruption of antagonistic regulators of the myeloid differentiation programme, such as the PRC1.1 component PCGF1, confers strong resistance to DOT1L inhibition, within a framework in which KAT6A, menin and DOT1L form a synergistic silencing hub.

   A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia · Aryal S, Curtiss BM, Zhou X, Lu R, Cheng C · Leukemia 40(5):996-1008 2026
   PMID 41882099DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. Shares senior authors with [E6], so this is the same group's programme extended to a second drug class rather than independent confirmation. AML only.

   ▸Evidence that argues against this (1)

   • Two resistance results from one laboratory, with no independent replication as of this cycle, is thinner support than the concordance implies. The strongest available check is that the dependency direction agrees in an entirely independent dataset, but that dataset cannot see resistance at all. Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
8. E8moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

   In the project's genome-wide KMT2A-rearranged selectivity scan of 17,728 genes across 1,208 cell lines (11 KMT2A-rearranged versus 43 other leukaemia lines), the PRC1.1 subunits score: PCGF1 difference +0.1448, rank 17,405, pan-essentiality -0.0384; BCOR +0.1019, rank 16,929, +0.0251; BCORL1 +0.0609, rank 15,515, +0.0771; RNF2 +0.0964, rank 16,819, -0.0474; KDM2B -0.0464, rank 3,765, -0.0404; SKP1 -0.0132, rank 7,404, -1.2813. MEN1 ranks 1 (-0.8656) and KMT2A ranks 11 (-0.5411) in the same scan.

   Genome-wide KMT2A-rearranged selectivity scan, 17,728 genes (DepMap Chronos via Open Targets) · Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
   ▸What this evidence cannot show

   All six rows read out of analyses/depmap-kmt2a-selective-scan-full/results.json on 2026-09-19 in a single pass, so no number here was typed from memory. RYBP is absent from the scan and has no row. Eleven KMT2A-rearranged lines, none infant-derived, AML-heavy. Single-gene knockouts cannot see paralogue-buffered requirements (RING1A for RNF2, BCOR for BCORL1 and vice versa), and SKP1's value is a floor effect.

   ▸Evidence that argues against this (1)

   • The orderly pattern this entry reads off the table - specific subunits anti-dependency, shared subunits neutral - could equally be produced by paralogue buffering alone, with no biology about restraint in it. Ring1a/Ring1b double deletion showed PRC1 catalysis IS required for MLL-AF9 leukaemogenesis, which is precisely the requirement a single-gene scan cannot detect, so the pattern must not be read as evidence that PRC1 activity is dispensable. Rossi A et al. 2016
9. E9strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   The PUFD domains of BCOR and BCORL1 differ in their ability to assemble with KDM2B: BCORL1 PUFD suffices, whereas BCOR PUFD alone does not stably assemble with KDM2B and requires residues N-terminal to PUFD; NMR shows the BCOR PUFD termini, critical for binding PCGF1 and KDM2B, are disordered, implying hierarchical assembly in which they become ordered on PCGF1 binding.

   Structure and Role of BCOR PUFD in Noncanonical PRC1 Assembly and Disease · Wong SJ, Senkovich O, Artigas JA, Gearhart MD, Ilangovan U, Graham DW, Abel KN, Yu T, Hinck AP, Bardwell VJ, Kim CA · Biochemistry 59(29):2718-2728 2020
   PMID 32628469DOI
   ▸What this evidence cannot show

   Abstract fetched and read on 2026-09-19; full text not read. Purified domains and NMR; the tumour relevance is asserted for BCOR internal tandem duplications in paediatric kidney and brain tumours, not leukaemia.

   ▸Evidence that argues against this (1)

   • The paralogue asymmetry is inferred across constructs and papers from one group rather than from a single side-by-side comparison, so it may reflect construct boundaries. If BCOR and BCORL1 turn out to be interchangeable after all, the caution this entry attaches to single-paralogue knockouts weakens considerably. Wong SJ et al. 2016
10. E10strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Genetic depletion of the H2A ubiquitin ligase subunits Ring1a and Ring1b in mice showed that PRC1 activity and H2AK119 monoubiquitination are required for the leukemogenic potential of both Hox-activating fusions such as MLL-AF9 and non-Hox-activating fusions, preventing differentiation of leukaemic cells.

    Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice · Rossi A, Ferrari KJ, Piunti A, Jammula S, Chiacchiera F, Mazzarella L, Scelfo A, Pelicci PG, Pasini D · Science Advances 2(10):e1600972 2016
    PMID 27730210DOI
    ▸What this evidence cannot show

    Abstract fetched and read on 2026-09-19; full text not read. Mouse, myeloid, MLL-AF9. Because both Ring1 paralogues are deleted, this establishes a requirement for PRC1 catalysis generally and says nothing about which PCGF flavour supplies it - PRC1.1 is not distinguished from canonical PRC1 here.

    ▸Evidence that argues against this (1)

    • This result is frequently cited as if it showed PRC1.1 is required in MLL-rearranged leukaemia. It does not: RING1A/B are shared by all six PRC1 complexes, and the PRC1.1-specific subunits score as anti-dependencies in the same disease. Attributing the Rossi phenotype to PRC1.1 would be a complex-level conflation. Gao Z et al. 2012
11. E11strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    KDM2B-PRC1.1 target promoters in mouse thymocytes carry high H2AK119ub1 and high H3K4me3 but low H3K27me3, are expressed at higher levels than non-targets, and PRC1.1 restrains excessive transcriptional activation by NOTCH1; loss of the KDM2B ZF-CxxC domain in haematopoietic cells causes lethal T-ALL, establishing PRC1.1 as a tumour suppressor in T-cell leukemogenesis.

    KDM2B in polycomb repressive complex 1.1 functions as a tumor suppressor in the initiation of T-cell leukemogenesis · Isshiki Y, Nakajima-Takagi Y, Oshima M, Aoyama K, Rizk M, Kurosawa S, Saraya A, Kondo T, Sakaida E, Nakaseko C, Yokote K, Koseki H, Iwama A · Blood Advances 3(17):2537-2549 2019
    PMID 31471323DOI
    ▸What this evidence cannot show

    Abstract fetched and read on 2026-09-19. Mouse thymocytes and human T-ALL: neither the lineage nor the driver matches KMT2A::AFF1.

    ▸Evidence that argues against this (1)

    • The same complex is reported as essential for human AML leukaemic stem cells in xenografts. A tumour-suppressor role in T-cell initiation and an essential role in myeloid maintenance cannot both be the general behaviour of PRC1.1, and no experiment has yet tested both phenotypes in one system. van den Boom V et al. 2016
12. E12strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Bcor loss-of-function in murine myeloid cells increased both proliferation and differentiation with upregulated Hox gene expression, reduced RING1B protein levels, and reduced H2AK119ub upstream of the upregulated HoxA genes.

    BCOR regulates myeloid cell proliferation and differentiation · Cao Q, Gearhart MD, Gery S, Shojaee S, Yang H, Sun H, Lin DC, Bai JW, Mead M, Zhao Z, Chen Q, Chien WW, Alkan S, Alpermann T, Haferlach T, Muschen M, Bardwell VJ, Koeffler HP · Leukemia 30(5):1155-65 2016
    PMID 26847029DOI
    ▸What this evidence cannot show

    Abstract fetched and read on 2026-09-19; full text not read. Normal and BCOR-mutant murine myeloid cells plus BCOR-mutant AML patient expression profiles; no KMT2A rearrangement selection, so the HoxA link here concerns myelopoiesis and not a fusion-driven HOXA programme.

    ▸Evidence that argues against this (1)

    • The direction conflicts with the KMT2A-rearranged resistance work, where PRC1.1 loss REDUCES monocytic differentiation signatures. Increased differentiation on BCOR loss in normal myeloid cells and decreased differentiation signature on BCOR loss in KMT2A-rearranged AML cannot both be the general effect, and neither study tested the other's system. Zhou X et al. 2024
13. E13moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The tethering of the BCOR-PRC1.1 enzymatic core to KDM2B is modulated by calcium and proceeds via liquid-liquid phase separation.

    Calcium modulates the tethering of BCOR-PRC1.1 enzymatic core to KDM2B via liquid-liquid phase separation · Chen R, Shen F, Zhang Y, Sun M, Dong Y, Yin Y, Su C, Peng C · Communications Biology 7(1):1112 2024
    PMID 39256555DOI
    ▸What this evidence cannot show

    Title, journal, year and DOI fetched from PubMed on 2026-09-19; the abstract was not read in this cycle and the claim is taken from the title only, so no cell type, calcium concentration or droplet parameter is asserted. This entry uses it solely to mark that a condensate description of PRC1.1 exists.

    ▸Evidence that argues against this (1)

    • A phase-separation description and the fixed four-component crystal structure are hard to hold together: if PRC1.1 recruitment is condensate-mediated and calcium-tuned, then the stoichiometric assembly in PDB 5JH5 describes one state rather than the working complex, and interface-directed reasoning about PRC1.1 inherits that limitation. RCSB Protein Data Bank; entry and polymer-entity alignment records queried via data.rcsb.org 2016

• ← related toBMI1 - the self-renewal gene that KMT2A fusions can do without, because HOXA9 covers for it at the same locus

  BMI1 is PCGF4 of CANONICAL PRC1; PRC1.1 uses PCGF1 - two different PCGF arms, and this graph treats the second as the central one

• ← part ofRNF2 (RING1B) — the one catalytic subunit shared by every PRC1 flavour, which is why the genetics point two ways at once

  catalytic H2AK119ub E3 ligase subunit; shared with all six PCGF-defined PRC1 complexes

• ← part ofBCORL1 — the BCOR paralogue that is in the only crystal structure of the PRC1.1 core, and is the one PRC1.1 subunit nobody has tested in KMT2A-rearranged leukaemia

  alternative corepressor arm; PUFD aa 1668-1785 modelled in PDB 5JH5

• ← part ofSKP1 — a pan-essential housekeeping adaptor that is also a structural subunit of PRC1.1, which makes it the one PRC1.1 member that can never be a target

  structural subunit; modelled aa 2-163 in PDB 5JH5 as the KDM2B partner

• part of →PCGF1 — the PRC1.1 scaffold whose LOSS causes menin-inhibitor resistance, so it is a restraint on the leukaemia rather than a dependency of it

  PCGF1 is the defining scaffold that makes this PRC1.1 rather than another PRC1 flavour

• part of →KDM2B — 513 potent ChEMBL rows that are mostly patent bins, and no structure of the domain they claim to inhibit

  ZF-CxxC DNA-binding subunit targeting non-methylated CpG islands

• part of →BCOR — the other side of the CBX8 conflict, and a target you would be inhibiting in the direction of disease

  corepressor arm; the subunit named in the KMT2A-rearranged menin-resistance screens

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

  loss of PCGF1 or BCOR reactivates bivalent noncanonical menin targets including MYC and confers menin-inhibitor resistance

• related to →MEN1 / menin — the adaptor the fusion cannot work without

  PRC1.1 and menin-KMT2A co-occupy a bivalent class of promoters; menin inhibition phenocopies polycomb disruption

• related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)

  NOT an interactome member: the documented relationship is promoter-level antagonism; no PRC1.1 subunit has been shown to contact a KMT2A fusion

• arises in →KMT2A-rearranged acute myeloid leukaemia in children and infants

  every functional PRC1.1 result in KMT2A-rearranged disease is AML; none is B-lineage

• ← supportsInteractome round 4: what was counted, what was written, what was rejected, and the two alias traps this beat fell into and caught

  subunit-level counts and dependency rows behind the complex-level PRC1.1 synthesis

• ← related toFour beats in a row were picked by noticing the same shape by hand; this is the instrument that finds it - 171 gene symbols named in six or more entries with no entry of their own

  the symbol collision: PRC1 is a mitotic spindle gene in HGNC

• causes →H2AK119ub - the mark every PRC1.1 claim in this graph rests on, named in fifteen entries and written in none until now

  PRC1.1 deposits this mark at non-methylated CpG islands via KDM2B targeting

• ← part ofRING1 (RING1A) - the paralogue that is not RING1B, and the reason a substring search for 'RING1' in this graph returns the wrong gene

  alternative catalytic RING subunit of PRC1.1 (and of every PRC1 flavour)

• ← part ofUSP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today

  integral PRC1.1 component with TRIM27; required for complex integrity and chromatin binding

• ← depends onA menin inhibitor does not only take something away - it causes PRC1.1 to put something on, and the drug needs the cell's own silencing machinery to work

  efficacy contingent on an intact host complex; PRC1.1 integrity is a candidate predictive biomarker

• ← part ofTRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited

  reported integral component; single-laboratory result, not independently reproduced

• ← related toPRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves

  PRC2.2 (JARID2/AEBP2) reads H2AK119ub1 and couples to PRC1; no leukaemia evidence distinguishes the subtypes here

• ← related toWhat fills the space: RING1B and BCOR arrive at the fusion's sites under BOTH drugs, but the DOT1L inhibitor puts them everywhere on the fusion's territory while the menin inhibitor puts them only in the quartile where the fusion is most completely evicted - and at Meis1 RING1B rises 16-fold

  measures RING1B, BCOR and KDM2B occupancy at fusion-held sites under both drugs

• ← part ofKDM2B, the PRC1.1 CpG-island recruiter, sits at the 99.7th percentile of its own distribution on the fusion's strongest sites in DMSO and does not gain share under either a menin inhibitor or a DOT1L inhibitor - it holds position while comparable bins drift down

  KDM2B is the CxxC-ZF addressing subunit of PRC1.1

• ← related toIn murine MLL-AF9, knocking out PCGF1 changes the menin inhibitor's effect on H3K79me2 by 0.0166 of a share ratio and the DOT1L inhibitor's by 0.0101 - both smaller than the 0.0584 two control cultures of the same line already differ by, so the mark's drug response runs outside PRC1.1

  H3K79me2's response to both a menin inhibitor and a DOT1L inhibitor runs outside PRC1.1: removing its PCGF1 subunit leaves both responses unchanged, while the published literature reports the same loss confers menin-inhibitor resistance transcriptionally

• ← related toBin the deposited H2AK119ub NTvKO 2 x 3 design: twelve files, three replicate conventions, public since 2025-11-23 and never analysed - it is the only route to the silencing clause of hyp-q117's prediction 5, it is the internal validation of the PCGF1 knockout this project's null depends on, and it carries a spread the H3K79me2 arm cannot

  the H2AK119ub antibody (NEB 8240S clone D27C4) cannot distinguish PRC1.1 from canonical PRC1 deposition, so the experiment's PRC1.1 attribution rests on the PCGF1 genotype and not on the reagent

• ← related toAt the 2 kb bins a menin inhibitor strips the most fusion from, both repressive marks GAIN and the active mark is LOST, monotonically in eviction depth (Spearman +1.000, +1.000 and -1.000) against a baseline-matched null that is flat to within 0.007 - the silencing clause of hyp-q117's prediction 5, measured for the first time

  the complex whose catalytic product is the readout

• ← testsFour matched input tracks, used for the two things an input is actually for: no chromosome-scale copy-number difference between the CRISPR clone and its control (max 1.0988, min 0.9470 in both processing states), and the knockout's H2AK119ub depletion from CpG islands is REAL because its own genomic DNA is enriched there, not depleted

  CpG-island localisation as the complex's targeting signature

• ← depends onThe chromatin exchange at a menin-inhibited fusion site, measured in one experiment: H2AK119ub and H3K27me3 in, H3K4me3 out, in proportion to how much fusion left - and PCGF1 loss attenuates the in-fill without abolishing it

  the complex whose product fills the vacated sites

• ← related toA PCGF1-null cell - a published resistance genotype - loses H3K79me2 at the most-evicted sites exactly as a control cell does (0.6123 against 0.5860), so the new stratified readout scores it as fully drug-engaged, and stratification does NOT close the resistance blind spot it was hoped to close

  PCGF1 is the PRC1.1-defining paralog

• ← part ofRYBP - the subunit that makes a variant PRC1 complex catalytically active, named by two entries in this graph and never written

  component of the BCOR/PRC1.1 complex in its founding purification

• ← testsTitrate PRC1.1 capacity against menin-inhibitor response, and measure H2AK119ub on the same timecourse as H3K79me2

  titrates PRC1.1 catalytic capacity rather than deleting a subunit