The H3K9 machinery's address at KMT2A is the PROMOTER, not the exon-11 breakpoint anchor: G9a, HP1a and KAP1 all read the top decile of active promoters there in MCF-7 and KAP1's peak replicates a K562 peak to 267 bp, while five proteins across five cell types are ORDINARY or absent at the anchor - so every H3K9-directed intervention this graph has discussed is aimed 52 kb from where the machinery is

[
  "The promoter address survives input normalisation: in an input-controlled ChIP or CUT&RUN in MCF-7, the KMT2A promoter remains above the 85th percentile of active-gene promoters for EHMT2, CBX5 and TRIM28 while the 90 kb gene body falls below the 60th.",
  "In a KMT2A-rearranged B-lineage cell (SEM or RS4;11), the same three proteins read above the 85th percentile of that cell's active-gene promoters at the KMT2A promoter and below the 75th percentile of that cell's own CTCF anchors at the 146 bp exon-11 window.",
  "A G9a/GLP inhibitor at prophylactic-equivalent exposure changes KMT2A transcript level by more than 1.3-fold while changing H3K9me1/me2 at the exon-11 anchor by less than 1.3-fold, in the same experiment.",
  "H3K9me1 or H3K9me2 at the KMT2A promoter is above the 75th percentile of active-gene promoters in any cell type where it is measured, while at the exon-11 anchor it is below the 50th."
]

[
  "exp-q116-the-h3k9-module-at-the-kmt2a-promoter-read-in-a-kmt2a-rearranged-cell-with-an-input-arm",
  "exp-q114-a-suv39h1-cutandrun-in-a-cd34-progenitor-and-a-kmt2a-rearranged-line"
]

[
  "ana-q116-the-h3k9-repressive-module-converges-on-the-kmt2a-promoter-in-mcf7-and-none-of-it-is-at-the-breakpoint",
  "ana-q116-kap1-has-a-called-peak-on-the-kmt2a-promoter-in-mcf7-and-none-within-52-kb-of-the-anchor",
  "ana-q116-trim28-comes-closer-to-firing-at-the-exon-11-anchor-than-anything-yet-and-the-specificity-clause-blocks-it",
  "ana-q116-g9a-sits-on-the-kmt2a-promoter-in-mcf7-and-is-ordinary-at-the-exon-11-anchor"
]

[
  "An INPUT-CONTROLLED ChIP or CUT&RUN in MCF-7 in which the KMT2A promoter falls BELOW the 75th percentile of active-gene promoters for EHMT2, CBX5 and TRIM28 after input normalisation kills the promoter half of this hypothesis outright. The promoter claim currently rests on a null (2,000 active-gene promoters) that re-bases the hyper-ChIPable-promoter artefact rather than removing it, and no input track exists in either deposit that holds these data.",
  "Any measurement placing an H3K9 writer, reader or scaffold ABOVE the 75th percentile of same-cell-type CTCF anchors at the 146 bp exon-11 window (GRCh38 chr11:118,488,614-118,488,760) in >= 60% of at least four tracks, with the median of the six non-anchor KMT2A intervals BELOW the 50th percentile in the same tracks, in any human cell type, kills the breakpoint half. PARTLY CASHED, CYCLE 68, AND IT CAME CLOSE: TRIM28 reached 90.62, 81.85 and 89.45 in three of four MCF-7 tracks - clearing the 60% clause - and failed on a six-non-anchor median of 65.87. The hypothesis survives on the specificity clause alone in that one antigen.",
  "A G9a/GLP inhibitor that moves H3K9me1 or H3K9me2 at the 146 bp exon-11 anchor by MORE than 1.5-fold while moving KMT2A transcript level by LESS than 1.3-fold, in a haematopoietic cell, refutes the therapeutic clause - because it would show the agent acts at the breakpoint rather than at the promoter. Neither measurement exists for any G9a agent in any cell type; drug-unc0642's in vivo result carries no pharmacodynamic measurement at all.",
  "A damage-state measurement (ionising radiation or a TOP2 poison, any timepoint) that places SUV39H1, SETDB1, EHMT2 or TRIM28 above the 75th percentile of same-cell-type CTCF anchors at the exon-11 window would not refute this hypothesis but would make it irrelevant, because it would mean the anchor address exists in the state that matters and every measurement behind this hypothesis is of the state that does not."
]

{
  "panel_median_kmt2a_gene_percentile": 61.39,
  "panel_median_kmt2a_promoter_percentile": 96.87,
  "per_antigen_median_promoter_percentile_vs_CTCF_anchors": {
    "TRIM28": 99.8,
    "CBX5_mut4E": 99.75,
    "KDM4B": 99.37,
    "KDM4C": 98.47,
    "CBX5_mut4A": 96.76,
    "CBX5": 96.65,
    "EHMT2": 95.83,
    "H3K9me3": 29.43
  },
  "reading": "every PROTEIN antigen reads 95.8-99.8 at the KMT2A promoter against CTCF anchors and only the histone mark (29.43) does not - so that statistic cannot discriminate between proteins at all, and every promoter claim in this beat rests on the ACTIVE-PROMOTER null instead"
}