GenemoderateQ37-histone-chaperones

SUPT6H (SPT6) - the histone chaperone that rides with RNA polymerase II, which puts it closer to the fusion's proposed mechanism than anything else in this beat

also called SUPT6H · SPT6 · SPT6H · hSPT6 · KIAA0162 · transcription elongation factor SPT6 · Q7KZ85

SPT6 travels with the enzyme that reads genes and puts the histones back after it has passed. A KMT2A fusion's whole proposed job is to force that enzyme through genes it should not be reading, so SPT6 is the chaperone working directly downstream of the fusion.

The same thing, for a scientist

SUPT6H (Q7KZ85, 1,726 aa) is the histone chaperone that binds RNA polymerase II throughout elongation. It is a subunit of the **activated Pol II-DSIF-PAF-SPT6 elongation complex** solved by cryo-EM [E1] - the same complex this graph already holds pieces of as `gene-supt4h1`/`gene-supt5h` (DSIF) and `gene-paf1`/`mechanism-paf1c-couples-elongation-to-h2bub` (PAF). **The structural entry point to this beat therefore already exists in the graph and had no chaperone attached to it.** Acute degradation separates two things that decades of yeast genetics had merged: **SPT6 is required for Pol II processivity and, unexpectedly, for termination - acute depletion causes readthrough at thousands of genes - while cryptic intragenic transcription appears only on LONG-TERM depletion and is therefore an accumulated epigenetic consequence rather than a direct function** [E2]. SPT6 is also a maintenance factor for centromeric CENP-A, preventing loss of old CENP-A nucleosomes during centromeric transcription [E3]. **In this disease it is invisible.** `(SUPT6H OR SPT6) AND (MLL OR KMT2A)` returns 0 [E4], and DepMap gives a difference of -0.035 at a pan-essentiality of **-1.915**, the second-deepest in this beat [E5].

Go deeper

The degron result is the important one, and it is a method lesson this graph should reuse

Targeted degradation of SPT6 split one gene's phenotype into two on the basis of timescale alone 2:

depletion	phenotype	interpretation
acute (hours)	loss of processivity; readthrough transcription at thousands of genes	direct elongation and termination function
long-term	cryptic intragenic transcription	accumulated chromatin damage, not a direct function

That is precisely the discrimination this graph needs for every chaperone in this beat, and for DOT1L itself. A gene knocked out for two weeks in a CRISPR screen is the long-term condition; every dependency number in this beat is of that kind. It is also the design that would separate 'the fusion needs continuous chaperone activity' from 'the cell falls apart when you remove a chaperone for a fortnight'.

The same logic applies to the clearance clock. If a DOT1L inhibitor's effect depends on histone replacement, the relevant experiment is a timed one, and SPT6 is the chaperone whose degron system already exists.

Facts and figures

uniprot	Q7KZ85
gene symbol	SUPT6H
length AA	1726
complex	activated Pol II-DSIF-PAF-SPT6 elongation complex
kmt2a literature records	0
subnuclear localization	HISTONE LOCUS BODY, in DROSOPHILA and conditionally - Spt6 was identified as a novel HLB component by RNAi and proteomics, and cytology of Mxc, Spt6, FLASH, Mute, U7 snRNP and the MPM-2 phosphoepitope showed sequential recruitment and hierarchical dependency for localisation to HLBs during development (PMID 21576393) [E_q95_supt6h_loc2]. Caveat carried on the entry: the HLB forms AT the replication-dependent histone gene cluster, so a chaperone travelling with elongating Pol II would appear there whenever those genes fire - the body-type address and the occupancy result may be one fact seen two ways, and nobody has asked whether Spt6 is retained when histone transcription is off. No mammalian HLB has been reported to contain SPT6, and no speckle, nucleolar or PML-body assignment exists in any organism.
localization shown for fusion	NO, and it is the cleanest 'nobody has looked' in this tranche: ZERO records for SUPT6H, SPT6 or SPT6H against the nine-term KMT2A/MLL fusion clause, from a 273-record gene clause [E_q95_supt6h_loc3]. This entry argues the localisation frame is wrong for this protein: SPT6's address is occupancy, so the missing measurement is an SPT6 chromatin-occupancy profile at HOXA in a KMT2A-rearranged cell with and without menin inhibition - a ChIP, not an image - and the same gap applies to SUPT5H and SUPT4H1.

graph neighbours already present

[
  "gene-supt5h",
  "gene-supt4h1",
  "gene-paf1",
  "protein-fact-complex"
]

functions

[
  "RNAPII processivity",
  "termination",
  "nucleosome reassembly behind Pol II",
  "CENP-A maintenance"
]

depmap

{
  "index_mean": -1.8419,
  "other_leukaemia_mean": -1.8069,
  "difference": -0.035,
  "pan_essentiality": -1.9151,
  "n_index": 11,
  "interpretation": "floor-compressed; not interpretable as selectivity"
}

depmap kmt2a selectivity

{
  "chronos_mean_kmt2a_rearranged": -1.8419,
  "chronos_mean_other_leukaemia": -1.8069,
  "difference": -0.035,
  "pan_essentiality_all_lines": -1.9151,
  "selectivity_rank": 4821,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

localization

{
  "CONSTITUTIVE": "NUCLEUS, on a single ECO:0000305 CURATOR INFERENCE with no experimental citation, no by-similarity chain and no motif rule - the weakest compartment evidence class in this graph [E_q95_supt6h_loc1]. UniProt tissue specificity: 'Ubiquitously expressed'.",
  "WHAT_LOCALISATION_MEANS_FOR_SPT6": "occupancy with a coordinate along a gene, not a compartment. In Drosophila, Spt5 and Spt6 colocalise at many transcriptionally active sites on polytene chromosomes, are recruited to heat-shock loci within TWO MINUTES in an HSF-dependent way, and Spt6 co-distributes with the largest Pol II subunit and with cyclin T (P-TEFb) at active sites [E_q95_supt6h_loc1]. The occupancy literature is 175 records against 36 for a localisation clause.",
  "systems": "Drosophila polytene chromosomes and embryos, Saccharomyces cerevisiae, Arabidopsis elongation complexes. NO mammalian compartment measurement of any kind."
}

cell type

{
  "measured_in": "NOTHING MAMMALIAN. Drosophila cells and embryos, budding yeast, Arabidopsis [E_q95_supt6h_loc1][E_q95_supt6h_loc2].",
  "expression": "UniProt: ubiquitously expressed - no cell-type handle.",
  "in_kmt2a_r": "ZERO records for the gene clause against the nine-term fusion clause, over three symbols, corroborating this entry's pre-existing data.kmt2a_literature_records of 0 [E_q95_supt6h_loc3]. DepMap is floor-compressed: index arm -1.84 against -1.81 in other leukaemia, pan-essentiality -1.92, which this entry already records as not interpretable as selectivity."
}

cell state

{
  "TRANSCRIPTIONAL_ACTIVATION_IS_THE_STATE_AND_IT_ACTS_IN_MINUTES": "Spt6 arrives at heat-shock loci within two minutes of induction and the recruitment requires HSF [E_q95_supt6h_loc1]. That is the fastest state-dependent repositioning in this tranche.",
  "S_PHASE": "the one body SPT6 has been placed in is the histone locus body, whose activity is S-phase-coupled [E_q95_supt6h_loc2] - so the body-associated pool, if it exists in mammals, would be phase-restricted.",
  "not_recorded": "no damage-induced or differentiation-dependent redistribution; nothing under menin inhibition."
}

localization bounded absence

{
  "date": "2026-09-22",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q95",
  "shape": "one [tiab] tag per term (rule 94); cytogenetic terms quoted (rule 95); querytranslation read back and stored (rule 90)",
  "absence_class": "never-measured",
  "queries": {
    "gene_clause_alone": {
      "query": "SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]",
      "count": 273,
      "querytranslation": "\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]"
    },
    "gene_AND_loc": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]) AND (localization[tiab] OR localisation[tiab] OR subcellular[tiab] OR immunofluorescence[tiab] OR nuclear[tiab] OR cytoplasmic[tiab] OR compartment[tiab])",
      "count": 36,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"localization\"[Title/Abstract] OR \"localisation\"[Title/Abstract] OR \"subcellular\"[Title/Abstract] OR \"immunofluorescence\"[Title/Abstract] OR \"nuclear\"[Title/Abstract] OR \"cytoplasmic\"[Title/Abstract] OR \"compartment\"[Title/Abstract])"
    },
    "gene_AND_subnuclear": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]) AND (\"nuclear speckle\"[tiab] OR \"nuclear speckles\"[tiab] OR nucleolus[tiab] OR nucleolar[tiab] OR \"PML body\"[tiab] OR \"PML bodies\"[tiab] OR \"nuclear matrix\"[tiab] OR \"Polycomb bodies\"[tiab] OR \"Polycomb body\"[tiab] OR subnuclear[tiab] OR \"nuclear bodies\"[tiab] OR \"nuclear body\"[tiab] OR chromocent*[tiab] OR heterochromat*[tiab])",
      "count": 8,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"nuclear speckle\"[Title/Abstract] OR \"nuclear speckles\"[Title/Abstract] OR \"nucleolus\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract] OR \"PML body\"[Title/Abstract] OR \"PML bodies\"[Title/Abstract] OR \"nuclear matrix\"[Title/Abstract] OR \"Polycomb bodies\"[Title/Abstract] OR \"Polycomb body\"[Title/Abstract] OR \"subnuclear\"[Title/Abstract] OR \"nuclear bodies\"[Title/Abstract] OR \"nuclear body\"[Title/Abstract] OR \"chromocent*\"[Title/Abstract] OR \"heterochromat*\"[Title/Abstract])"
    },
    "gene_AND_fusion": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL1\"[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab] OR \"MLL-ENL\"[tiab] OR \"MLL-AF10\"[tiab] OR \"t(4;11)\"[tiab] OR \"t(11;19)\"[tiab])",
      "count": 0,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL1\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"MLL-ENL\"[Title/Abstract] OR \"MLL-AF10\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract] OR \"t 11 19\"[Title/Abstract])"
    },
    "gene_AND_loc_AND_fusion": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]) AND (localization[tiab] OR localisation[tiab] OR subcellular[tiab] OR immunofluorescence[tiab] OR nuclear[tiab] OR cytoplasmic[tiab] OR compartment[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL1\"[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab] OR \"MLL-ENL\"[tiab] OR \"MLL-AF10\"[tiab] OR \"t(4;11)\"[tiab] OR \"t(11;19)\"[tiab])",
      "count": 0,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"localization\"[Title/Abstract] OR \"localisation\"[Title/Abstract] OR \"subcellular\"[Title/Abstract] OR \"immunofluorescence\"[Title/Abstract] OR \"nuclear\"[Title/Abstract] OR \"cytoplasmic\"[Title/Abstract] OR \"compartment\"[Title/Abstract]) AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL1\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"MLL-ENL\"[Title/Abstract] OR \"MLL-AF10\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract] OR \"t 11 19\"[Title/Abstract])"
    },
    "gene_AND_subnuclear_AND_fusion": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab] OR SPT6H[tiab]) AND (\"nuclear speckle\"[tiab] OR \"nuclear speckles\"[tiab] OR nucleolus[tiab] OR nucleolar[tiab] OR \"PML body\"[tiab] OR \"PML bodies\"[tiab] OR \"nuclear matrix\"[tiab] OR \"Polycomb bodies\"[tiab] OR \"Polycomb body\"[tiab] OR subnuclear[tiab] OR \"nuclear bodies\"[tiab] OR \"nuclear body\"[tiab] OR chromocent*[tiab] OR heterochromat*[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL1\"[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab] OR \"MLL-ENL\"[tiab] OR \"MLL-AF10\"[tiab] OR \"t(4;11)\"[tiab] OR \"t(11;19)\"[tiab])",
      "count": 0,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"nuclear speckle\"[Title/Abstract] OR \"nuclear speckles\"[Title/Abstract] OR \"nucleolus\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract] OR \"PML body\"[Title/Abstract] OR \"PML bodies\"[Title/Abstract] OR \"nuclear matrix\"[Title/Abstract] OR \"Polycomb bodies\"[Title/Abstract] OR \"Polycomb body\"[Title/Abstract] OR \"subnuclear\"[Title/Abstract] OR \"nuclear bodies\"[Title/Abstract] OR \"nuclear body\"[Title/Abstract] OR \"chromocent*\"[Title/Abstract] OR \"heterochromat*\"[Title/Abstract]) AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL1\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"MLL-ENL\"[Title/Abstract] OR \"MLL-AF10\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract] OR \"t 11 19\"[Title/Abstract])"
    },
    "spt6_loc": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab]) AND (localization[tiab] OR localisation[tiab] OR immunofluorescence[tiab] OR \"nuclear speckle\"[tiab] OR subnuclear[tiab])",
      "count": 15,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"localization\"[Title/Abstract] OR \"localisation\"[Title/Abstract] OR \"immunofluorescence\"[Title/Abstract] OR \"nuclear speckle\"[Title/Abstract] OR \"subnuclear\"[Title/Abstract])"
    },
    "spt6_occupancy": {
      "query": "(SUPT6H[tiab] OR SPT6[tiab]) AND (ChIP[tiab] OR occupancy[tiab] OR \"gene bodies\"[tiab] OR elongation[tiab])",
      "count": 175,
      "querytranslation": "(\"SUPT6H\"[Title/Abstract] OR \"SPT6\"[Title/Abstract]) AND (\"ChIP\"[Title/Abstract] OR \"occupancy\"[Title/Abstract] OR \"gene bodies\"[Title/Abstract] OR \"elongation\"[Title/Abstract])"
    }
  },
  "corroborates": "data.kmt2a_literature_records = 0 on this entry, measured by an earlier beat on a narrower symbol set; this run widens the symbol set to SUPT6H, SPT6 and SPT6H and the count is still 0.",
  "title_check": "gene_AND_subnuclear, 8 records, 0 of 8 a mammalian compartment measurement - the Drosophila HLB paper, two Drosophila polytene occupancy papers, yeast SPT5/SPT6 genetics including the 1990 SPT6 cloning paper (an acidic nuclear protein), two plant elongation-complex papers and a CTR9 neurodevelopmental paper.",
  "occupancy_versus_localisation": {
    "occupancy clause": 175,
    "localisation clause": 36,
    "ratio": "4.8x",
    "reading": "this protein's literature is about where it acts along genes, not which compartment it is in"
  }
}

How this could bite us back

SUPT6H is required for productive transcription of protein-coding genes in every cell; at a DepMap pan-essentiality of -1.92 across 1,208 lines it is among the least selective targets imaginable and a general block has no window.
Long-term SPT6 loss causes cryptic intragenic transcription and, in other work, R-loop formation, replication stress and senescence - so a chronic partial block would create genome instability in a paediatric patient on a timescale no trial endpoint measures.
SPT6 maintains centromeric CENP-A; interfering with it risks centromere identity and chromosome missegregation, which in a childhood cancer is the worst available class of late effect.

Still open

Does acute SPT6 degradation change H3K79me2 at KMT2A-fusion target genes faster than a DOT1L inhibitor does? The degron exists, the antibody exists, and the experiment would directly test whether elongation-coupled histone exchange is the clearance route.
Does a KMT2A fusion alter SPT6 occupancy at its target genes? The graph has the fusion's ChIP and the field has SPT6 ChIP; nobody has overlapped them.
SPT6 prevents loss of old histones during transcription. Does the fusion's forced elongation overwhelm that retention at HOXA, and is the resulting exchange what sets the local H3K79 valency?

Every source behind this entry (8)

E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The structure of the complete Pol II-DSIF-PAF-SPT6 transcription complex has been solved and reveals RTF1 allosteric activation; SPT6 is an integral component of the activated elongation complex.
Structure of complete Pol II-DSIF-PAF-SPT6 transcription complex reveals RTF1 allosteric activation. · Vos SM, Farnung L, Linden A, et al. · Nature Structural & Molecular Biology 2020
PMID 32541898 DOI
What this evidence cannot show
Record fetched from efetch 2026-09-20 for title, authors and DOI; abstract read, full text not read and no PMCID in the record. Cryo-EM of a reconstituted complex from purified components - established for the architecture, and a reconstituted complex is not a measurement of composition in a leukaemic cell. **No residue coordinates or domain spans are stored in this entry**, because this project requires spans to be derived by aligning a fetched entity sequence to a freshly fetched UniProt sequence and that was not done.
Evidence that argues against this (1)
- A structure shows what can assemble, not what is rate-limiting. The same beat's DepMap data show SUPT6H is required in essentially every cell line at -1.92, which means its presence in the elongation complex says nothing about whether a KMT2A fusion depends on it more than any other cell does. Oncofusion knowledge graph (internal analysis) 2026
E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Targeted protein degradation of SPT6 in human cells shows SPT6 is crucial for RNA polymerase II processivity and therefore for productive transcription of protein-coding genes, and has a vital role in termination - acute depletion induced readthrough transcription for thousands of genes; long-term depletion induced cryptic intragenic transcription as seen earlier in yeast, but this was NOT observed on acute depletion and is therefore attributable to accumulated epigenetic perturbations in the prolonged absence of SPT6.
Targeted protein degradation reveals a direct role of SPT6 in RNAPII elongation and termination. · Narain A, Bhandare P, Adhikari B, et al. · Molecular Cell 2021
PMID 34233157 DOI
What this evidence cannot show
Abstract read from efetch 2026-09-20; full text not read (PMC8354102 exists). Human cell line with an engineered degron; established within that system. The mathematical modelling supporting the processivity conclusion is not assessed here. Not a leukaemic or KMT2A-rearranged system.
Evidence that argues against this (1)
- A degron removes the protein; a drug occupies a site. The acute/long-term distinction this paper draws is about protein presence and does not map directly onto pharmacological inhibition, where partial occupancy over weeks is the realistic exposure and would produce neither of the two regimes cleanly. Zumer K et al. 2021
E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Spt6 spatially and temporally coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells; Spt6 binds directly to dCENP-A, and phosphomimetic dCENP-A mutants show reduced retention while non-phosphorylatable dCENP-A accumulates at the centromere.
Spt6 is a maintenance factor for centromeric CENP-A. · Bobkov GOM, Huang A, van den Berg SJW, et al. · Nature Communications 2020
PMID 32522980 DOI
What this evidence cannot show
Abstract read from efetch 2026-09-20; full text not read (PMC7287101 exists). Drosophila plus human cells; the mechanistic detail is Drosophila. Cited here because it is the clearest demonstration that SPT6's job during transcription is to STOP old histones being lost - the retention side of turnover, which is the side the clearance-clock argument needs and almost never measures.
Evidence that argues against this (1)
- CENP-A is a specialised variant at a specialised locus and generalising a centromeric retention function to gene bodies is an extrapolation this entry is making, not one the paper makes. Narain A et al. 2021
E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
As of 2026-09-20, PubMed returns 0 records for '(SUPT6H OR SPT6) AND (MLL OR KMT2A)' and 0 for 'SPT6 AND DOT1L'; '(SUPT6H OR SPT6) AND leukemia' returns 2, neither about SPT6 in a KMT2A-rearranged cell on title check (a CDK9/CDK12-13 apoptosis study and a 2012 JMJD3 elongation paper).
NCBI E-utilities esearch over PubMed for SUPT6H/SPT6 against KMT2A, MLL, DOT1L and leukaemia, with title checking, run 2026-09-20 · US National Library of Medicine 2026
What this evidence cannot show
Query translations captured; no [UID] terms. Titles fetched in full. Bounded by the symbols SUPT6H and SPT6; the alias SPT6H and the spelling hSPT6 were not separately crossed, and a paper using only 'the elongation complex' framing would be missed - the failure mode that hid the MLL/TAF-I result from every symbol query in this beat.
Evidence that argues against this (1)
- This graph already holds DSIF and PAF entries for the same elongation complex that SPT6 belongs to, so the biology is present in the graph while the chaperone is not. A zero here reflects what has been written about, not what is mechanistically connected. Vos SM et al. 2020
E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
In DepMap CRISPR gene effect, SUPT6H's mean effect is -1.842 in 11 KMT2A-rearranged leukaemia lines against -1.807 in 43 other leukaemia lines (difference -0.035) at a pan-essentiality of -1.915 across 1,208 lines. SUPT6H is UniProt Q7KZ85 (SPT6H_HUMAN), transcription elongation factor SPT6, 1,726 amino acids.
Is any histone chaperone or variant-exchange gene selectively required in KMT2A-rearranged leukaemia lines, and does the answer survive a lineage split? · Oncofusion knowledge graph (internal analysis) 2026
What this evidence cannot show
DepMap run 2026-09-20; UniProt fetched the same day with `gene_primary` requested and read back per rule 62 (one reviewed human record, primary symbol SUPT6H). **At a pan-essentiality of -1.92 the group difference is floor-compressed and uninterpretable as selectivity**; it is reported so the absence of a signal is on the record. The FACT subunits sit in the same regime (SUPT16H -1.763, SSRP1 -1.271).
Evidence that argues against this (1)
- The degron result shows SPT6's acute and chronic phenotypes are different, and a two-week CRISPR screen measures only the chronic one. A pan-essentiality score for SPT6 is therefore a statement about accumulated chromatin damage as much as about the elongation function, and is the wrong instrument for asking whether a fusion needs it. Narain A et al. 2021
E_q95_supt6h_loc1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
SUPT6H's UniProt compartment is a CURATOR INFERENCE AND NOTHING ELSE: Q7KZ85 carries exactly one location value, 'Nucleus', on a single ECO:0000305 - no experimental citation, no by-similarity chain to another species, no motif rule. That is the weakest class of compartment evidence in this graph, weaker than SGF29's cross-species ECO:0000250 or EP400's PROSITE motif rule, on a 1,726-residue histone chaperone that travels with elongating RNA polymerase II.
UniProtKB Q7KZ85 (SPT6H_HUMAN), SUBCELLULAR LOCATION comments with evidence codes and sources, fetched live 2026-09-22 · UniProt Consortium · Databases 2026
What this evidence cannot show
A statement about the database record. ECO:0000305 is the code brief rule 91 item 4 singles out as worth flagging - it is what tranche 4 found for SMARCD2 and called unusual for a BAF subunit. Nobody disputes that SPT6 is nuclear; the record simply contains no measurement, and UniProt's tissue specificity line ('Ubiquitously expressed') offers no compartment either.
Evidence that argues against this (1)
- THE DEEPER POINT IS THAT A COMPARTMENT IS THE WRONG QUESTION FOR THIS PROTEIN AND A CURATOR INFERENCE MAY BE THE HONEST ANSWER. SPT6's position is defined by what it is attached to: in Drosophila, Spt5 and Spt6 colocalise at a large number of transcriptionally active chromosomal sites on polytene chromosomes, are recruited to heat-shock loci within two minutes of a heat shock in an HSF-dependent manner, and Spt6 co-distributes with the largest subunit of Pol II and with cyclin T, a P-TEFb subunit, at sites of active transcription. That is occupancy with a coordinate along a gene, and it moves within minutes. 'Nucleus' is trivially true of it and describes nothing; the quantity that matters is which genes, at what phase of the transcription cycle - which is why this entry records occupancy separately rather than treating it as a localisation. Andrulis ED et al. 2000
E_q95_supt6h_loc2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
SPT6 does have one NAMED SUBNUCLEAR BODY, and it is cross-phylum: an RNAi and proteomic screen in Drosophila identified the transcription elongation factor suppressor of Ty 6 (Spt6) as a novel component of the HISTONE LOCUS BODY, the nuclear body involved in expression of replication-dependent histone genes, alongside a homologue of mammalian NPAT encoded by multi sex combs; cytology of Mxc, Spt6 and the known HLB components FLASH, Mute, U7 snRNP and the MPM-2 phosphoepitope demonstrated sequential recruitment and hierarchical dependency for localisation to HLBs during development.
Drosophila histone locus bodies form by hierarchical recruitment of components. · White AE, Burch BD, Yang XC, Gasdaska PY, Dominski Z, Marzluff WF, Duronio RJ · J Cell Biol 2011
PMID 21576393 DOI
What this evidence cannot show
Drosophila melanogaster, cell culture and embryos - brief rule 73 applies and the claim names the system. Hierarchical recruitment means Spt6's presence in the body is CONDITIONAL on other components, so this is another complex-dependent compartment rather than an intrinsic address, and no mammalian histone locus body has been reported to contain SPT6.
Evidence that argues against this (1)
- AND THE HLB RESULT MAY BE THE SAME FACT AS THE OCCUPANCY RESULT SEEN THROUGH A DIFFERENT INSTRUMENT, WHICH WOULD MAKE IT LESS OF A SEPARATE COMPARTMENT THAN IT APPEARS. The histone locus body forms AT the replication-dependent histone gene cluster - it is a nuclear body defined by a genomic locus that is being transcribed at high rate in S phase. A chaperone that travels with elongating Pol II would be expected to appear there whenever those genes fire, without needing any body-specific affinity, and the paper's own finding of hierarchical dependency is consistent with either reading. So the defensible statement is that SPT6 is present in a transcription-defined body in Drosophila, not that SPT6 has a body-type address. Distinguishing them requires asking whether Spt6 is retained at the locus when histone transcription is off, which the hierarchy experiments do not test. Andrulis ED et al. 2000
E_q95_supt6h_loc3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
Bounded 2026-09-22 and it CORROBORATES this entry's own pre-existing figure: the gene clause over SUPT6H, SPT6 and SPT6H returns 273 records and intersects the nine-term KMT2A/MLL fusion clause at ZERO - matching data.kmt2a_literature_records, which this entry already records as 0 and which was measured independently by an earlier beat on a narrower symbol set. With a localisation clause the gene clause returns 36 and with a subnuclear clause 8; the occupancy sub-query (ChIP, occupancy, 'gene bodies', elongation) returns 175, which is 4.8 times the localisation clause and is where this protein's literature actually lives.
NCBI E-utilities esearch db=pubmed; every count stored with the querytranslation read back, in data.localization_bounded_absence · NCBI E-utilities · Databases 2026
What this evidence cannot show
Titles and abstracts only; supporting figures not searched (rule 80). SPT6 as a bare token retrieves yeast and Drosophila work, which widens rather than narrows the net behind the zero. The 8 subnuclear records were title-checked and none is a mammalian compartment measurement: they are the Drosophila HLB paper, the Drosophila polytene occupancy papers, yeast genetics including the 1990 SPT6 cloning paper describing an acidic nuclear protein, plant elongation-complex papers and a CTR9 neurodevelopmental-disorder paper.
Evidence that argues against this (1)
- A ZERO THAT AGREES WITH AN EARLIER INDEPENDENT ZERO IS WORTH MORE THAN EITHER, AND IT ALSO SHOWS WHERE THE REAL GAP IS - WHICH IS NOT LOCALISATION. This project's central mechanistic proposal is that the KMT2A fusion forces productive elongation through genes that should be silent, and SPT6 is the chaperone that reassembles nucleosomes behind that polymerase; it is DepMap floor-compressed at -1.84 in the index arm against -1.81 elsewhere, so dependency cannot discriminate. The measurement that would matter is an SPT6 chromatin-occupancy profile at HOXA in a KMT2A-rearranged cell, compared with and without menin inhibition - a ChIP, not an image. This entry's neighbours SUPT5H and SUPT4H1 are in the same position, so the gap is axis-wide rather than gene-specific, and no amount of immunofluorescence closes it. Jonas F et al. 2023

Connected to

part of →SUPT5H (SPT5) — the pausing factor the KMT2A field has never studied, and the counted absence that undercuts 'the fusion hijacks pause release'
both subunits of the activated Pol II-DSIF-PAF-SPT6 elongation complex
part of →PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein
both subunits of the activated Pol II-DSIF-PAF-SPT6 elongation complex
related to →Mechanism class 1 — chromatin and elongation hijack (KMT2A-r, NUP98-r)
the chaperone that reassembles nucleosomes behind the polymerase the fusion forces forward
analogous to →FACT (SPT16-SSRP1) - the chromatin arm of transcription elongation, and a clean negative result for the KMT2A::AFF1 interactome
two elongation-coupled histone chaperones travelling with Pol II
← related toCSNK2A1 (casein kinase 2 alpha) - the one kinase that turns up three separate times in KMT2A biology
NON-HISTONE SUBSTRATE WITH A MARK-LEVEL CONSEQUENCE: CK2 phosphorylates the histone chaperone Spt6, and that phosphorylation is required to suppress H3 turnover and cryptic sense/antisense transcription; CK2 depletion raises H3K56 acetylation replication-independently. Yeast; the human SUPT6H has no equivalent experiment.
related to →Transcription factories and Pol II clusters - no KMT2A::AFF1 imaging, condensate evidence for SEC and MLL-ENL, and 3D-FISH that actively contradicts the factory story for t(4;11)
SPT6's address is OCCUPANCY, not a compartment: in Drosophila, Spt5 and Spt6 colocalise at many active sites on polytene chromosomes, arrive at heat-shock loci within TWO MINUTES in an HSF-dependent way, and Spt6 co-distributes with the largest Pol II subunit and with cyclin T of P-TEFb (PMID 11040217). UniProt's only value is 'Nucleus' on a bare ECO:0000305 curator inference (Q95 2026-09-22)
related to →'AF4 bodies' - a named subnuclear compartment that is non-nucleolar and coincident with no known nuclear structure, and the one place a KMT2A fusion has been shown to move a partner
The one NAMED body SPT6 has ever been placed in is the Drosophila HISTONE LOCUS BODY, by RNAi and proteomics with hierarchical recruitment (PMID 21576393) - and it may be the occupancy result seen through another instrument, because the HLB forms at the histone gene cluster being transcribed. No mammalian body assignment exists for SPT6 in any organism (Q95 2026-09-22)
← related toELP4 (PAXNEB) - a required subunit of Elongator, the one partner of the seven with a genuine histone-acetyltransferase connection, and the one whose fusion supplies only its last 43 residues
both are Pol II-associated elongation factors with no mark of their own whose meaningful address is occupancy along a gene, not a compartment
← analogous toTMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
the two clean NOT-APPLICABLE epigenetics calls in this corpus, both justified on domain architecture rather than defaulted to