ANP32E - the eviction chaperone: the only protein in this beat whose job is to take a histone variant OUT of chromatin
also called ANP32E · acidic leucine-rich nuclear phosphoprotein 32 family member E · Cpd1 · LANP-L · Q9BTT0
Every other chaperone here puts histones in. ANP32E takes one particular variant back out, which is the half of turnover that nobody measures and that this project's clock argument silently assumes.
The same thing, for a scientist
ANP32E (Q9BTT0, 268 aa) is the specific H2A.Z removal chaperone and a member of the p400/TIP60 exchange complex. It grips a short region of the H2A.Z docking domain through an H2A.Z-interacting domain (ZID); the 1.48 A crystal structure of ANP32E-ZID with H2A.Z-H2B supports eviction of H2A.Z/H2B from the nucleosome stabilised by an extension of the H2A.Z C-terminal alpha-helix; and in ANP32E-null cells H2A.Z is enriched, redistributed and accumulated at enhancers and insulators genome-wide [E1]. **Its conceptual importance to this beat exceeds its evidence.** Turnover is deposition plus eviction, and every rate argument in `mechanism-h3k79-turnover-and-dilution` and in this beat's own mechanism entry is written as if deposition were the whole of it. ANP32E is the existence proof that eviction is separately encoded and separately regulated - and **there is no known equivalent eviction chaperone for H3.3**, which is why the H3.3 half of the argument has no eviction term at all. In this disease: `ANP32E AND leukemia` returns 6 records and **all six are about ANP32B**, a different family member, on title check [E2]. DepMap difference **+0.093**, pan-essentiality -0.276 [E3].
The missing eviction term, stated as a gap
| variant | deposition chaperone | eviction chaperone |
|---|---|---|
| H2A.Z | VPS72/YL1 with SRCAP or p400/TIP60 | ANP32E |
| H3.3 | HIRA/HUCA, ATRX/DAXX, ASF1B | none identified |
For H3.3 the field describes eviction as a passive consequence of polymerase passage, remodeller action or replication - not as a chaperone-catalysed step. If that asymmetry is real, then H3.3 turnover rate is set almost entirely by how often something pushes the nucleosome out, which in a gene body is transcription itself. That is the version of the clearance-clock argument this beat ends up defending: in a transcribing gene body, the clock is the transcription rate.
If the asymmetry is instead a gap in knowledge, an H3.3 eviction chaperone would be a much better intervention point than any deposition factor here, because removing histones is the step whose blockade would PROLONG a mark rather than the step whose blockade prolongs it by starving supply. Neither possibility has been tested.
| uniprot | Q9BTT0 |
|---|---|
| gene symbol | ANP32E |
| length AA | 268 |
| function | H2A.Z-H2B eviction chaperone; member of the p400/TIP60 complex |
| counterpart | VPS72/YL1 (deposition) |
| leukaemia literature records title checked | 0 |
| family hazard | ANP32B dominates the 'ANP32E AND leukemia' result set; a raw count of 6 has a real value of 0 |
depmap — the numbers behind the chart
{
"index_mean": -0.1943,
"other_leukaemia_mean": -0.2872,
"difference": 0.0929,
"pan_essentiality": -0.2756,
"n_index": 11
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.1943,
"chronos_mean_other_leukaemia": -0.2872,
"difference": 0.0929,
"pan_essentiality_all_lines": -0.2756,
"selectivity_rank": 16734,
"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."
}- Blocking eviction would trap variant histones in chromatin rather than removing them; in ANP32E-null cells H2A.Z accumulates at enhancers and insulators, which is a genome-wide redistribution rather than a targeted effect.
- Because ANP32E removes rather than deposits, inhibiting it is the one intervention in this beat that would SLOW turnover in the opposite direction - and slower turnover still means slower clearance of a mark with no eraser.
- The literature for this gene in leukaemia is a counted zero contaminated by a same-family paralogue, so any claim that it is 'unstudied' also means nobody knows what happens when it is perturbed in a blood cell.
- Is there an H3.3 eviction chaperone? The absence of one is either a real asymmetry that makes transcription itself the clock, or a gap in the field - and this beat could not distinguish them.
- Does ANP32E-mediated H2A.Z eviction occur at KMT2A-fusion target genes, and does it change under menin or DOT1L inhibition?
- The ANP32E/VPS72 relationship is reported as both cooperative and opposing in a 2026 preprint. Does that peer-review, and does it change which of the two is the rate-limiting step?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
ANP32E is a specific H2A.Z chaperone and a member of the p400/TIP60 histone-exchange complex; it interacts with a short region of the H2A.Z docking domain via an H2A.Z-interacting domain (ZID); the 1.48 A crystal structure of ANP32E-ZID with the H2A.Z/H2B dimer supports a mechanism of H2A.Z/H2B eviction from the nucleosome stabilised by extension of the H2A.Z C-terminal alpha-helix; and ChIP-seq in ANP32E-null cells shows genome-wide enrichment, redistribution and accumulation of H2A.Z at enhancers and insulators.
ANP32E is a histone chaperone that removes H2A.Z from chromatin. · Obri A, Ouararhni K, Papin C, et al. · Nature 2014What this evidence cannot show
Abstract read from efetch 2026-09-20; full text not read (no PMCID in the record). Mouse and human cells plus crystallography; established for the biochemistry and the null-cell redistribution. Not leukaemia, not KMT2A. **No residue spans stored**, per this project's rule that a span must be derived by aligning a fetched entity sequence to a freshly fetched UniProt sequence.
Evidence that argues against this (1)
- A 2026 preprint reports cooperative and OPPOSING functions of ANP32E and VPS72 at gene promoters, so the clean 'ANP32E evicts, YL1 deposits' division is incomplete. The preprint has not been peer reviewed and is recorded as a bound on the model rather than as a result. Murphy P et al. 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
As of 2026-09-20, PubMed returns 6 records for 'ANP32E AND leukemia' and on title check none of them is about ANP32E: four concern ANP32B (a PU.1-activating B-ALL suppressor, a caspase-3 substrate study, a caspase-3-resistant form, and a myeloid apoptosis study), one is a childhood-leukaemia single-cell prognostic survey and one a multiple-myeloma cytogenetics study. 'ANP32E AND (MLL OR KMT2A)' was not returned in any beat query with a title-checked hit.
NCBI E-utilities esearch over PubMed for ANP32E against leukaemia, with title checking of all returned records, run 2026-09-20 · US National Library of Medicine 2026What this evidence cannot show
Query translation captured; no [UID] term. All 6 titles fetched in full. **This is a worked example of alias/family contamination in the direction of INFLATION**: a raw count of 6 reads as a small but real literature and the real number is zero. The contaminating gene is a same-family paralogue, ANP32B, which is exactly the class of confusion rule 63 covers.
Evidence that argues against this (1)
- A zero here does not mean the biology is absent from the disease - Tip60, which works in the same p400/TIP60 complex as ANP32E, has a direct MLL-fusion paper. The absence is of this gene in this literature, not of H2A.Z exchange in this leukaemia. Yamagata K et al. 2021
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
ANP32E is UniProt Q9BTT0 (AN32E_HUMAN), acidic leucine-rich nuclear phosphoprotein 32 family member E, 268 amino acids, with no alias gene symbols in the reviewed record; the family member ANP32A is a separate record (P39687, 249 aa) whose aliases include LANP and PHAP1. In DepMap, ANP32E's mean effect is -0.194 in 11 KMT2A-rearranged leukaemia lines against -0.287 in 43 other leukaemia lines (difference +0.093) at a pan-essentiality of -0.276.
UniProtKB Q9BTT0 (AN32E_HUMAN), Acidic leucine-rich nuclear phosphoprotein 32 family member E, 268 aa · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026What this evidence cannot show
UniProt fetched 2026-09-20 with `gene_primary` requested and read back per rule 62 (one reviewed human record, primary symbol ANP32E); ANP32A fetched the same way for the family comparison. The DepMap numbers are from this beat's own run of the same day and are a NEGATIVE result: ANP32E is slightly less required in the index arm and is not required anywhere. No permutation null.
Evidence that argues against this (1)
- A near-zero pan-essentiality means the knockout is close to neutral, so both group means are approximately nothing and the difference between them carries little information in either direction. Reported for completeness rather than as evidence. Oncofusion knowledge graph (internal analysis) 2026
ANP32E evicts H2A.Z-H2B from the nucleosome
ANP32E is a member of the p400/TIP60 exchange complex
eviction chaperone; preferentially binds H2A.Z-H2B and removes it from +1 nucleosomes