Oncofusion

start / graph / absence-no-resection-factor-localised-at-the-kmt2a-locus

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q32-brca1-hr-licensing

No BRCA1, BARD1, EXO1, DNA2, HP1-gamma or KDM5A has ever been localised at the KMT2A locus, in any cell type: 21 queries, every querytranslation read back, 0 on-topic records - and the absence splits THREE ways by class, which is what decides what it costs to close

also called resection factors at the KMT2A locus · BRCA1 at 11q23 · the counted absence for the HR licensing layer · scope: the six named proteins only - NOT RPA (RPA at the 11q23 hotspot after etoposide: PMID 21048951)

Nobody has ever measured where the DNA-repair machinery sits on the KMT2A gene, in any cell, in any published paper. For two of these proteins the public data already exist and nobody has looked; for four of them no data exist at all.

The same thing, for a scientist

**The question.** Q110 asked whether any H3K9me3 writer or reader had been localised at the *KMT2A* locus and found the answer was no for SUV39H1, SETDB1 and CBX5/HP1-alpha. This entry asks the same question one layer down the cascade, for the **resection-licensing layer** that Q110's beat did not cover: **BRCA1, BARD1, EXO1, DNA2, CBX3/HP1-gamma and KDM5A**. **The answer is no, for all six.** Twenty-one PubMed queries run live on 2026-09-22, every `querytranslation` read back, every zero required to carry a non-empty translation plus `warninglist.outputmessages = ['No items found.']`, and every non-zero count title-checked by esummary. **Zero records place any of these six proteins at *KMT2A*, at its breakpoint cluster region, or at 11q23.** **But the absence is not one absence, and the difference is the actionable part** [E2, E3]: | protein | ENCODE ChIP-seq | blood line among them | absence class | what closes it | |---|---:|---|---|---| | **BRCA1** | **7** | **K562, GM12878** | `measured-not-analysed` | compute, no wet work | | **CBX3** (HP1-gamma) | **4** | **K562, GM12878** | `measured-not-analysed` | compute, no wet work | | **KDM5A** | 3 | **none** (A549, H1, HepG2) | `never-measured` in blood; `measured-not-analysed` elsewhere | a ChIP in a blood cell | | **BARD1** | 0 TF ChIP-seq (**but the target record EXISTS - 200**; corrected 2026-09-22) | - | `never-measured` for occupancy | antibody + experiment | | **EXO1** | 0 (no target record) | - | `never-measured` | and ChIP is the wrong assay anyway | | **DNA2** | 0 (no target record) | - | `never-measured` | same | **Two of the six can be answered this week from data already on a public server.** That is the single most useful sentence in this entry. **A fourth class applies to all six and is worth naming: `measured-not-searched`.** The cascade is damage-conditional and minutes-scale. Every ENCODE dataset above is from an **undamaged** cultured cell. So even the two `measured-not-analysed` cases can only answer the *resting-state* question - and under the model in `mechanism-ctcf-primes-repressive-chromatin-for-brca1-bard1-at-a-break` the resting-state answer is expected to be negative and is uninformative. The damage-state question is `never-measured` for all six, in every cell type. **The instrument was controlled and one control failed instructively.** Rule-67 positive controls through the **identical** `SYMBOL[tiab] AND TOKEN[tiab]` shape: `CTCF[tiab] AND KMT2A[tiab]` = **7** and `RAD21[tiab] AND KMT2A[tiab]` = **5**, so the shape returns ones. But `TOP2B[tiab] AND KMT2A[tiab]` = **0** through the same shape, although the TOP2B-KMT2A relationship is one of the best-established facts in this disease - because that literature writes *MLL* and *topoisomerase II*. **The instrument works and the vocabulary is the binding constraint** (rule 71), and every count here inherits that limit.

Facts and figures
scriptno script - this is a query and archive census with every count and querytranslation recorded inline
statusrun
run date2026-09-22
run byQ32-brca1-hr-licensing
what is absentAny measurement of BRCA1, BARD1, EXO1, DNA2, CBX3/HP1-gamma or KDM5A OCCUPANCY at the KMT2A gene, its breakpoint cluster region, or its exon-11 CTCF/cohesin element (GRCh38 chr11:118,488,159-118,489,206), in any cell type, in the published literature.
what is NOT absent(1) Measurements of these proteins at OTHER loci and at engineered breaks - abundant. (2) Measurements of the H3K9 MARK at the KMT2A locus - those exist (GSE210480 in RPE via Q108; ENCODE K562 H3K9me1). (3) CTCF and cohesin occupancy at the KMT2A exon-11 element - well established in this graph. This absence is about the RESECTION LAYER specifically and is a different question from Q110's, which covered the writers and HP1-alpha.
absence classnever-measured
absence class noteThe headline class is the LEAST severe of the six, deliberately, because it is the one that determines the next action: for BRCA1 and CBX3 the data exist and nobody has looked. The per-protein breakdown below is the real content and must be read instead of the headline for any protein other than those two.
result summarySix proteins, 21 queries, 0 records placing any of them at the KMT2A locus in any cell type. Three absence classes across the six. Two of the six (BRCA1, CBX3) are closable with compute against existing ENCODE data in blood-lineage cells. All six are never-measured in the damage state that the mechanism actually predicts.
inputs
[
  "NCBI E-utilities esearch over PubMed, db=pubmed, retmode=json",
  "NCBI E-utilities esummary for every title check",
  "ENCODE Portal experiment search, assay_title=TF ChIP-seq, status=released, per target label",
  "IntAct REST findInteractions for O00255 (menin) and Q03164 (KMT2A)"
]
absence class per protein
{
  "BRCA1": "measured-not-analysed - 7 released ENCODE TF ChIP-seq experiments including K562 and GM12878, never read at this locus. Closable with compute.",
  "CBX3": "measured-not-analysed - 4 released ENCODE experiments including K562 and GM12878, never read at this locus. Closable with compute.",
  "KDM5A": "never-measured in a blood cell (ENCODE's 3 experiments are A549, H1 and HepG2); measured-not-analysed in lung, embryonic stem and liver cells. The stricter class is recorded because the graph's question is about a haematopoietic cell.",
  "BARD1": "CORRECTED 2026-09-22 - measured-not-analysed for ENCODE metadata purposes, never-measured for occupancy. BARD1 HAS an ENCODE target record (/targets/BARD1-human/ 200) and two released CRISPR RNA-seq experiments; what it lacks is a released TF ChIP-seq experiment. The occupancy absence stands, the 'no target record' reason for it does not.",
  "EXO1": "never-measured - no ENCODE target record; and ChIP-seq is arguably the wrong assay class, since resection is measured by ssDNA-resection qPCR, END-seq or BLESS at a defined break.",
  "DNA2": "never-measured - no ENCODE target record; same assay-class caveat as EXO1.",
  "ALL_SIX_in_the_damage_state": "never-measured. Every existing dataset is from an undamaged cultured cell, and the cascade is damage-conditional. No damage-state occupancy measurement exists for any of these proteins at this locus in any cell type."
}
queries run 2026 09 22
{
  "instrument": "NCBI E-utilities esearch over PubMed. Every querytranslation was read back from the response. Every zero was required to carry a NON-EMPTY translation plus warninglist.outputmessages = ['No items found.'] before being recorded; no zero in this table came back with an empty translation.",
  "query_form": "one [tiab] tag per term, never the grouped (A OR B)[tiab] form (rule 94); every cytogenetic term quoted (rule 95)",
  "locus_conjunctions_all_zero": {
    "BARD1[tiab] AND KMT2A[tiab]": 0,
    "BARD1[tiab] AND 11q23[tiab]": 0,
    "BRCA1[tiab] AND \"t(4;11)\"[tiab]": 0,
    "EXO1[tiab] AND KMT2A[tiab]": 0,
    "EXO1[tiab] AND MLL[tiab]": 0,
    "DNA2[tiab] AND KMT2A[tiab]": 0,
    "DNA2[tiab] AND MLL[tiab]": 0,
    "HP1gamma[tiab] AND MLL[tiab]": 0,
    "KDM5A[tiab] AND 11q23[tiab]": 0,
    "RBP2[tiab] AND MLL[tiab]": 0
  },
  "one_quoted_translocation_check": "BRCA1[tiab] AND \"t(4;11)\"[tiab] translated to '\"BRCA1\"[Title/Abstract] AND \"t 4 11\"[Title/Abstract]' - the quoted form survived as a phrase, as rule 95 requires. The UNQUOTED form was never run.",
  "nonzero_counts_all_title_checked_to_zero_on_topic": {
    "BRCA1[tiab] AND KMT2A[tiab]": {
      "count": 5,
      "records": {
        "27894958": "PARP inhibitors in TCF3-HLF-positive leukaemia - a different fusion, no KMT2A locus measurement",
        "31630891": "prenatal onset syndromic short stature exome sequencing - off topic",
        "33853832": "Recruitment of KMT2C/MLL3 to DNA damage sites, PARP inhibitor sensitivity - a DIFFERENT KMT2 family member, and the nearest near-miss in the whole sweep",
        "38050610": "oral submucous fibrosis cancerization, Hainan Island - off topic",
        "40678837": "nasopharyngeal carcinoma genomic profiling - off topic"
      }
    },
    "BRCA1[tiab] AND MLL[tiab]": {
      "count": 8,
      "records": {
        "19704708": "BARD1 may be renamed ROW1 because it functions mainly as a REPRESSOR OF WUSCHEL1 - ARABIDOPSIS, an identifier collision",
        "24448499": "germline and somatic variants in ovarian cancer - off topic",
        "25079327": "DNA-damage-induced differentiation of leukaemic cells - no BRCA1 locus measurement",
        "27894958": "as above",
        "29301143": "PSA velocity in prostate cancer screening - off topic",
        "31111759": "C-terminal BRE in MLL-AF9 AML cells and chemosensitivity - MLL-AF9, no BRCA1 localisation",
        "31590683": "epigenetic synthetic lethality approaches in cancer therapy - review",
        "38968834": "menin signaling and therapeutic targeting in BREAST cancer - review"
      }
    },
    "BRCA1[tiab] AND 11q23[tiab]": {
      "count": 4,
      "records": {
        "10571946": "ATM family cancer incidence - off topic",
        "11486176": "primary mammary small-cell carcinoma, 2 cases - off topic",
        "25483710": "BRCA1, PARP1 and gammaH2AX in AML as olaparib response biomarkers - protein levels, no locus",
        "36635772": "CTP synthase 2 and BRCA1 in chronic lymphocytic leukaemia - 11q23 here is the CLL deletion region (ATM), NOT the KMT2A breakpoint"
      },
      "the_11q23_trap": "11q23 is the cytoband of KMT2A AND of ATM, and in the CLL literature '11q23 deletion' means the ATM region. Two of the four hits use 11q23 in that sense. A count of BRCA1 x 11q23 is therefore not a count of BRCA1 x KMT2A even before title-checking."
    },
    "BARD1[tiab] AND MLL[tiab]": {
      "count": 2,
      "records": {
        "19704708": "the Arabidopsis BARD1/ROW1 paper - off topic",
        "37974198": "epigenetic CRISPR screen identifying ASH2L in glioblastoma - off topic"
      }
    },
    "CBX3[tiab] AND KMT2A[tiab]": {
      "count": 1,
      "records": {
        "39823827": "CCDC32/CBX3 secondary fusion in a KMT2A::AFDN AML patient - CBX3 as a FUSION PARTNER, not as a protein at the KMT2A locus. Recorded in gene-cbx3 E5."
      }
    },
    "KDM5A[tiab] AND KMT2A[tiab]": {
      "count": 14,
      "note": "NOT individually title-checked beyond confirming that none is a KMT2A-locus localisation study; most are expected to concern NUP98::KDM5A, a different question. This is recorded as a partially-checked count rather than presented as clean."
    },
    "BRCA1[tiab] AND breakpoint[tiab] AND leukemia[tiab]": {
      "count": 1,
      "records": {
        "32277283": "therapy-related acute leukaemia in germline BRCA1-mutated HBOC patients after topoisomerase II-directed therapy - the only genuinely on-beat record in the entire sweep, and it is a CLINICAL association, not a localisation. Recorded in gene-brca1 E4."
      }
    },
    "BRCA1[tiab] AND \"breakpoint cluster region\"[tiab]": {
      "count": 1,
      "records": {
        "40294979": "miRNAs in periodontitis and pancreatic cancer - off topic. 'Breakpoint cluster region' here is BCR the gene."
      }
    }
  },
  "rule_67_positive_controls_through_the_identical_shape": {
    "CTCF[tiab] AND KMT2A[tiab]": 7,
    "RAD21[tiab] AND KMT2A[tiab]": 5,
    "verdict": "the SYMBOL[tiab] AND TOKEN[tiab] shape returns ones, so no zero in this table is a composition artefact."
  },
  "the_control_that_FAILED_and_why_it_is_the_most_important_line_here": {
    "TOP2B[tiab] AND KMT2A[tiab]": 0,
    "querytranslation": "\"TOP2B\"[Title/Abstract] AND \"KMT2A\"[Title/Abstract]",
    "warninglist": "No items found.",
    "why_this_matters": "TOP2B and KMT2A are one of the best-established relationships in this entire disease and the symbol pair returns a clean, confident zero - because the literature writes 'MLL' and 'topoisomerase II'. This is rule 71 demonstrated live on this project's own central fact. The instrument is not broken; the VOCABULARY is the bound. Every zero in this entry is accurate as a measurement and none of them can be promoted to 'nobody has ever looked' without a vocabulary search that this beat did not run.",
    "what_that_licenses_and_does_not": "It licenses: 'no title or abstract using these current gene symbols reports this'. It does NOT license: 'no such measurement exists'."
  },
  "bare_operand_checks_rule_67_step_2": {
    "EXO1[tiab]": 1055,
    "DNA2[tiab]": 709,
    "BARD1[tiab]": 867,
    "CBX3[tiab]": 219,
    "MLL[tiab]": 6328,
    "KMT2A[tiab]": 1653,
    "why_recorded": "EXO1 x MLL is an empty intersection of a 1,055-record set with a 6,328-record set. Rule 67 says two large sets with an empty intersection is a claim needing its own evidence, so the operands are stated rather than hidden."
  },
  "name_lists_actually_tried_rule_70": {
    "CBX3": [
      "CBX3",
      "HP1gamma"
    ],
    "KDM5A": [
      "KDM5A",
      "RBP2"
    ],
    "BRCA1": [
      "BRCA1"
    ],
    "BARD1": [
      "BARD1"
    ],
    "EXO1": [
      "EXO1"
    ],
    "DNA2": [
      "DNA2"
    ],
    "NOT_tried_and_this_is_a_real_limit": "HP1-gamma with a hyphen, HP1G, HECH, CBX3's protein-name forms; JARID1A and RBBP2 for KDM5A; EXOI and HEX1 for EXO1; DNA2L for DNA2; RNF53 for BRCA1. This project has previously undercounted a literature TENFOLD by keying to the current symbol (the septin case), so the incompleteness of these name lists is the single largest weakness of this absence."
  },
  "bound_class": "titles and abstracts only. Rule 80 applies with full force: a BRCA1 or HP1-gamma ChIP track over KMT2A in a supporting figure of some paper would be invisible to all 21 queries, and the measurements a mechanism graph wants are usually supporting panels. This bound was not closed by opening candidate full texts."
}
archive census 2026 09 22
{
  "instrument": "ENCODE Portal, type=Experiment, assay_title=TF ChIP-seq, status=released, per target label, counted from the @graph length with biosample term names collected",
  "counts": {
    "BRCA1": {
      "n": 7,
      "biosamples": [
        "GM12878",
        "H1",
        "HeLa-S3",
        "HepG2",
        "K562"
      ]
    },
    "CBX3": {
      "n": 4,
      "biosamples": [
        "GM12878",
        "HCT116",
        "K562"
      ]
    },
    "CBX1": {
      "n": 2,
      "biosamples": [
        "HepG2",
        "K562"
      ]
    },
    "CBX5": {
      "n": 4,
      "biosamples": [
        "GM12878",
        "H1",
        "HepG2",
        "K562"
      ]
    },
    "KDM5A": {
      "n": 3,
      "biosamples": [
        "A549",
        "H1",
        "HepG2"
      ]
    },
    "CTCF": {
      "n": 502,
      "biosamples": [
        "182 distinct biosamples including bone marrow, HL-60, K562, Loucy, DND-41 and primary B and T cells"
      ]
    },
    "TRIM28": {
      "n": 5,
      "biosamples": [
        "HEK293",
        "K562"
      ]
    },
    "SETDB1": {
      "n": 5,
      "biosamples": [
        "HEK293",
        "HepG2",
        "K562"
      ]
    },
    "BARD1": {
      "n": 0,
      "note": "CORRECTED 2026-09-22. Previously read 'HTTP 404 on the target.label facet - no ENCODE target record exists'. FALSE. /targets/BARD1-human/ returns HTTP 200 and the 404 was a property of the assay_title=TF+ChIP-seq filter, so it described the query and not the protein. BARD1 has an ENCODE target record and two released CRISPR RNA-seq experiments; what it lacks is a released TF ChIP-seq experiment, which is the narrower and true statement. RAD50 behaves identically (200 bare, 404 filtered); EXO1, DNA2, SUV39H1 and RBBP8 are genuine 404s on both endpoints."
    },
    "EXO1": {
      "n": 0,
      "note": "HTTP 404 - no target record"
    },
    "DNA2": {
      "n": 0,
      "note": "HTTP 404 - no target record"
    },
    "SUV39H1": {
      "n": 0,
      "note": "HTTP 404 - no target record; independently matches Q110's census"
    },
    "RBBP8": {
      "n": 0,
      "note": "HTTP 404 - no target record. CtIP, the short-range resection nuclease, has no ENCODE occupancy data either"
    }
  },
  "cross_check_against_Q110": "Q110 counted the same facet one day earlier and reported SETDB1 5, CBX5 4, CBX1 2, CBX3 4, EHMT2 3, TRIM28 5 and SUV39H1 0. Every overlapping figure matches. This is a reproducibility check on the same endpoint, not an independent confirmation.",
  "archives_NOT_swept": "GEO individual depositions, ChIP-Atlas, ReMap, PRIDE, and - most importantly for EXO1 and DNA2 - any resection-mapping archive (END-seq, BLESS, ssDNA-seq in the AsiSI/DIvA system). A DIvA resection dataset covering chr11q23 would answer part of this question with no wet work and was NOT queried. That is a named, unclosed, cheap check and it is recorded as such rather than left implicit."
}
ABSENCE CLASS CHANGED cycle 63
{
  "from": "measured-not-analysed",
  "to": "never-measured",
  "why": "this entry classed BRCA1 and CBX3 as measured-not-analysed because ENCODE data existed and nobody had analysed it. Cycle 63 analysed it - 13 of 13 tracks, zero peaks, no signal above a class-matched null - so the public data is now spent. There is no remaining dataset that can advance this question for ANY of the six proteins, which is what never-measured means here.",
  "and_its_own_headline_sentence_is_now_false": "the entry called 'two of the six can be answered this week' its single most useful sentence. They were answered, and the answer was no, so the sentence no longer points anywhere. The 21 queries and the literature bound are unaffected and remain correct.",
  "what_this_costs": "the cheap route is gone. Advancing this question now requires wet work - ChIP in a damage state in a haematopoietic cell - which is the experiment absence-no-damage-state-occupancy-measurement-for-any-resection-factor-at-the-kmt2a-locus now carries.",
  "reported_by": "Q35; verified by the king against the beat's per-track table"
}
How this could bite us back
  • The cheapest way to close two of these six is a re-analysis of existing ENCODE BRCA1 and CBX3 data at chr11:118,436,000-118,526,000 in K562 and GM12878 - and a clean negative from it would be uninformative, because the model predicts the signal only after a break. Anyone running it should pre-register that reading, or the negative will be quoted as a refutation it is not.
  • Four of the six absence classes rest on one consortium's target facet. If a ChIP-Atlas sweep later finds a BARD1 or KDM5A dataset in a blood cell, the classes move and the cost estimates in this entry move with them - so this entry should be re-run, not quoted, after any archive sweep.
Still open
  1. Run the ENCODE re-analysis: is BRCA1 or CBX3 enriched at the KMT2A exon-11 CTCF element (GRCh38 chr11:118,488,159-118,489,206) or across the breakpoint cluster region in K562 or GM12878, above the local chr11 background? Two proteins, four datasets, two blood lines, no wet work, and nobody has ever looked.
  2. Does any deposited AsiSI/DIvA resection or END-seq dataset cover chr11q23? If an AsiSI site lies in or near the breakpoint cluster region, damage-state resection at this graph's locus may already be measurable from public data - the single highest-value unexecuted check this beat leaves.
  3. Do the incomplete name lists hide anything? JARID1A, RBBP2, EXOI, HEX1, DNA2L, RNF53 and HP1G were not searched, and the TOP2B control shows exactly how a symbol-keyed sweep fails on this disease's literature.
  4. Should IntAct's failure to curate either 2026 cascade paper be reported as a curation request? Both are open-access in PMC, both report direct protein contacts with mapped interfaces, and this graph's interactome coverage metrics cannot see either of them.
Every source behind this entry (4)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Twenty-one PubMed queries run live on 2026-09-22, with every querytranslation read back and every zero required to carry a non-empty translation plus warninglist 'No items found.', return zero records placing BRCA1, BARD1, EXO1, DNA2, CBX3 or KDM5A at the KMT2A locus, its breakpoint cluster region or 11q23. The zero conjunctions are BARD1 x KMT2A, BARD1 x 11q23, BRCA1 x "t(4;11)", EXO1 x KMT2A, EXO1 x MLL, DNA2 x KMT2A, DNA2 x MLL, HP1gamma x MLL, KDM5A x 11q23 and RBP2 x MLL. The non-zero counts were title-checked by esummary: BRCA1 x KMT2A 5, BRCA1 x MLL 8, BRCA1 x 11q23 4, BARD1 x MLL 2, CBX3 x KMT2A 1, BRCA1 x breakpoint x leukemia 1, BRCA1 x "breakpoint cluster region" 1 - and none is a localisation at this locus. Rule-67 positive controls through the identical SYMBOL[tiab] AND TOKEN[tiab] shape return CTCF x KMT2A 7 and RAD21 x KMT2A 5.

    NCBI E-utilities esearch and esummary over PubMed, db=pubmed, retmode=json, 21 queries with querytranslation read back for each · National Center for Biotechnology Information · NCBI Entrez Programming Utilities 2026
    What this evidence cannot show

    Titles and abstracts only (rule 80) - a ChIP track over KMT2A in a supporting figure would be invisible to every query, and this bound was not closed by opening candidate full texts. The name lists are incomplete and this is the largest weakness: JARID1A, RBBP2, EXOI, HEX1, DNA2L, RNF53, HP1G, HECH and hyphenated HP1-gamma forms were NOT searched, and this project has previously undercounted a literature tenfold by keying to a current symbol. The KDM5A x KMT2A count of 14 was not individually title-checked. 11q23 is ambiguous between the KMT2A band and the CLL/ATM deletion region and two of four hits used the latter sense.

    Evidence that argues against this (2)
    • TOP2B[tiab] AND KMT2A[tiab] returns 0 through the identical query shape, with a non-empty translation and 'No items found.', although the TOP2B-KMT2A relationship is central to this disease and is heavily cited in this very graph. So this query shape demonstrably produces a clean false NEGATIVE-as-conclusion whenever the field's vocabulary differs from the current symbols, and every zero in this entry carries that limitation. The absence recorded here is an absence in the current-symbol literature, not in the literature. National Center for Biotechnology Information 2026
    • SCOPE BOUNDARY - THE ID IS WIDER THAN THE CLAIM. The id says 'any resection factor'; the claim is scoped by its own fields to the named proteins (BRCA1, BARD1, EXO1, DNA2, CBX3/CBX1, KDM5A). RPA is NOT among them, and RPA binding at the 11q23 translocation breakpoint hotspot after etoposide HAS been measured: ATM deficiency raised RAD51 and also RPA and INO80 binding there (PMID 21048951, 2010; the abstract confirms the RPA binding, the assay format was read from full text by the Q192 agent and not re-verified here). Do not quote this entry's id as covering RPA or any other recruited resection factor. The id was NOT renamed: it has many inbound references and public URLs, and the title and fields are already scoped. PLoS One 2010
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    CORRECTED 2026-09-22. Previously read 'HTTP 404 on the target.label facet - no ENCODE target record exists'. FALSE. /targets/BARD1-human/ returns HTTP 200 and the 404 was a property of the assay_title=TF+ChIP-seq filter, so it described the query and not the protein. BARD1 has an ENCODE target record and two released CRISPR RNA-seq experiments; what it lacks is a released TF ChIP-seq experiment, which is the narrower and true statement. RAD50 behaves identically (200 bare, 404 filtered); EXO1, DNA2, SUV39H1 and RBBP8 are genuine 404s on both endpoints.

    What this evidence cannot show

    One consortium, one assay facet. GEO individual depositions, ChIP-Atlas, ReMap and every resection-mapping archive were NOT swept, so four of these 'never-measured' calls could be overturned by queries that were not run - and for EXO1 and DNA2 a TF ChIP-seq facet is close to the wrong place to look, since resection is measured by END-seq, BLESS or ssDNA qPCR. A 404 is read here as 'no target record', which is what the API's behaviour means but is a different negative from a searched zero. K562 is CML blast crisis and GM12878 an EBV-transformed B-lymphoblastoid line; neither is KMT2A-rearranged and neither is a fetal progenitor.

    Evidence that argues against this (1)
    • This project has already produced three independent false negatives about GEO from three different query forms for a SuperSeries that in fact had four subseries and 79 SRA experiments. Bounding four 'never-measured' calls on one consortium's target facet is the same shape of reasoning, and the honest position is that these four are never-measured IN ENCODE and unbounded elsewhere. NCBI Gene Expression Omnibus; ChIP-Atlas 2026
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Even the two closable cases can only answer the resting-state question, because the cascade is damage-conditional: in U2OS and HEK-293T, CTCF recruits HP1-gamma, KAP1, SUV39H1, SETDB1 and KDM5A to DSBs, enabling rapid and transient BRCA1/BARD1 accumulation and downstream EXO1/DNA2 recruitment, and HP1-gamma is described as rapidly and transiently recruited. Every ENCODE dataset in E2 is from an undamaged cultured cell, so a re-analysis at the KMT2A locus tests occupancy in the condition under which the model predicts no signal.

    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, Jeong JH, Kang MA, Lee JS · Nucleic Acids Research 2026
    What this evidence cannot show

    U2OS and HEK-293T only; the transience is established there and is assumed here to transfer, which it may not. The inference that a resting-state ENCODE re-analysis would be uninformative is MY reading of the model, not a statement the paper makes - and it is exactly the kind of reasoning that can be used to explain away any negative result, so it is recorded as a prediction to be pre-registered rather than as a reason not to run the analysis. DOI taken from PubmedData/ArticleIdList only.

    Evidence that argues against this (1)
    • A resting-state positive would be highly informative even under this model - it would falsify the 'no constitutive address' half of `hyp-the-writer-reaches-the-kmt2a-anchor-only-through-ctcf-and-only-after-the-break`. So the analysis is worth running regardless, and the argument above must not be used to discourage it: it bounds how a NEGATIVE may be read, and says nothing about a positive. Q110-h3k9me3-writer-layer 2026
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Neither menin nor KMT2A has a curated interaction with any member of either HR-licensing cascade, and the check was spike-controlled. Querying IntAct REST findInteractions on 2026-09-22 returns 137 interactions and 65 distinct molecules for menin (O00255) and 376 interactions and 173 distinct molecules for KMT2A (Q03164). Searching both molecule lists for BRCA1, BARD1, CBX3, CBX1, CBX5, KDM5A, EXO1, DNA2, CTCF, RBBP8, MRE11, NBN, PALB2, BRCA2, SMARCAD1, TRIM28, SUV39H1, SETDB1 and SETD2 returns NONE of them. The spike control passed: MEN1 and KMT2A each appear in the other's list (15 and 16 records respectively) and PSIP1/LEDGF appears in both, so the query form and the parsing both work.

    What this evidence cannot show

    The REST endpoint was used rather than PSICQUIC, as rule 93 requires. Processed-chain identifiers were NOT queried separately - KMT2A's taspase1 fragments Q03164-PRO_0000390949 and -PRO_0000390950 file their interactions separately and were not fetched here, so this is a floor. The absence of a curated row is a statement about IntAct's curation, not about biology: PMID 42578372 reports menin binding gammaH2A.X and recruiting SETD2, and PMID 42475683 reports CTCF binding BARD1, and NEITHER is curated in IntAct - so both cascades are `measured-not-curated` and any IntAct-derived coverage metric in this graph is structurally blind to them.

    Evidence that argues against this (1)
    • This is a curation gap presenting as a biological absence, which is the failure mode rule 93 documents - PSICQUIC returned no direct-interaction record for the menin-KMT2A contact while REST returned seven. Here even REST returns nothing for interactions that are published in Nucleic Acids Research in 2026, because IntAct has not curated either paper. Anyone reading 'menin does not interact with the HR machinery' off this row would be reading a fact about IntAct's backlog. Lian A et al. 2026
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