YY1 - the enhancer-promoter looping factor that recovers KMT2A in a 109-transcription-factor BioID screen
also called Yin Yang 1 · YIN-YANG-1 · NF-E1 · UCRBP · INO80S · Transcriptional repressor protein YY1
YY1 is a transcription factor that physically clips an enhancer to the gene it controls, holding the loop that lets a distant switch reach a promoter. When a 2022 study tagged 109 human transcription factors and listed everything each one brushed past, KMT2A turned up in YY1's neighbourhood - one row, in kidney cells, and nobody has checked it in a leukaemia.
The same thing, for a scientist
YY1 (HGNC:12856, ENSG00000100811, UniProt P25490, 414 aa, 14q32.2) is a ubiquitously expressed zinc-finger transcription factor that binds active enhancers and promoter-proximal elements and dimerises to hold enhancer-promoter loops; deleting YY1 sites or depleting the protein disrupts looping and gene expression [E2]. It enters this project's core-complex interactome through one curated row: IntAct IM-28767 from Goos et al. 2022, **MI:1314 proximity-dependent biotin identification**, MI:2364 proximity, MI:1060 spoke expansion, **YY1 bait / KMT2A prey**, MI-score 0.27, host `HEK293 Flp-In` [E1][E3]. That is proximity in an over-expressed heterologous system, not a contact: BioID biotinylates whatever comes within roughly 10 nm of the ligase, and this graph's reading of the same deposition records KMT2A as prey of **eleven** of the 109 TF baits [E1]. YY1 is nonetheless the member of that eleven with the most specific prior reason to sit near a KMT2A complex - it is a proposed core component of the INO80 remodelling complex [E4] and is localised to the **nuclear matrix** by experiment [E4], the compartment KMT2A's SET-domain-bearing complexes are classically fractionated into.
What the interaction record actually is
One IntAct row, IM-28767, deposited 2022-01-14, last updated 2026-01-11. Detection MI:1314 proximity-dependent biotin identification (BioID); interaction type MI:2364 proximity; expansion MI:1060 spoke; experimental roles MI:0496 bait (YY1) / MI:0498 prey (KMT2A); host organism taxid:9606(Homo sapiens HEK293flp-in embryonic kidney cell); curator annotation figure legend: Supp. Table 1; MI-score 0.27 3.
BioID proximity is not binding. The biotin ligase labels proteins within a labelling radius while the bait is over-expressed for hours; two proteins in the same condensate, the same chromatin neighbourhood or the same abundant nuclear pool will label each other without ever touching. Any use of this row that says YY1 binds KMT2A is an inflation. The honest reading is: in over-expressing embryonic kidney cells, KMT2A is within labelling distance of YY1.
Why YY1 is not just one of eleven
This graph already records that eleven TF baits in this screen recover KMT2A - EN1, NHLH1, ELF1, ELF2, FEV, KLF12, KLF3, YY1, MYC, NFIX and NFYC 1. A reader is right to ask what distinguishes YY1 from a promiscuous prey signal.
Two things, and neither is proof. (i) Compartment. UniProt assigns YY1 to the nucleus matrix on experimental evidence 4 - a subnuclear address, not just 'nucleus', and the one classically associated with the insoluble chromatin fraction KMT2A complexes partition into. Of the eleven, YY1 is the one with a matrix call. (ii) Function. YY1 holds enhancer-promoter loops 2, and the defining activity of a KMT2A fusion is inappropriate, sustained elongation at a small set of target promoters whose enhancers are known. A looping factor and an elongation-driving fusion at the same promoters is a mechanistically coherent proposal, which is exactly why it needs a real experiment rather than a screen row.
YY1 is also the mammalian functional analogue of Drosophila Pho, the Polycomb-response-element binding factor, which is the reason it recurs in chromatin literature; this entry does not cite that relationship to a primary source and therefore does not rest on it.
Cell type, cell state and what has never been measured
Cell type of the observation: HEK293 Flp-In embryonic kidney. Not haematopoietic. Not KMT2A-rearranged. No B-lineage or infant context anywhere in the record for this pair.
Never measured: whether YY1 is near KMT2A::AFF1 rather than wild-type KMT2A; whether the proximity survives in SEM, RS4;11 or MV4-11; whether YY1 occupies the HOXA cluster or any other fusion target in a KMT2A-rearranged cell; whether YY1 depletion changes fusion target expression. Every one of those is a gap, not a negative.
Other fusion families
Nobody has looked in any fusion. The row is wild-type KMT2A in HEK293. This graph mentions YY1 in entries for MSL2, KDM6A, KDM6B, HCFC1 and the LDB1::KMT2A fusion, but this beat did not verify a YY1 result in any other fusion family and asserts none.
| hgnc ID | HGNC:12856 |
|---|---|
| symbol | YY1 |
| ensembl gene ID | ENSG00000100811 |
| uniprot | P25490 |
| length AA | 414 |
| chromosomal location | 14q32.2 |
| identifier provenance | HGNC REST fetch/symbol/YY1 and UniProtKB P25490 both retrieved live 2026-09-23. The alias 'DELTA' was checked against the corpus and produced 55 false-positive prose matches and no entry collision - a worked example of why a short alias needs word-boundary matching. |
| subnuclear location | nuclear matrix - the only one of the eleven TF baits recovering KMT2A in this screen with a subnuclear compartment call in UniProt |
| cell type of the observation | HEK293 Flp-In embryonic kidney - not haematopoietic, not KMT2A-rearranged |
| epigenetic role | Enhancer-promoter loop factor (PMID 29224777); proposed core component of the INO80 remodelling complex (UniProt). |
| shown for fusion | NO - nobody has looked in any fusion. The proximity row is wild-type KMT2A in HEK293 Flp-In. |
| evidence class | single publication, single method, spoke-expanded BioID proximity, no orthogonal validation of the pair |
prev and alias symbols
[ "NF-E1", "DELTA", "UCRBP", "YIN-YANG-1", "INO80S" ]
interaction with project baits
[
{
"bait": "KMT2A",
"bait_uniprot": "Q03164",
"partner_experimental_role": "bait",
"scaffold_experimental_role": "prey",
"method": "MI:1314 proximity-dependent biotin identification",
"interaction_type": "MI:2364 proximity",
"expansion": "MI:1060 spoke",
"mi_score": 0.27,
"imex": "IM-28767",
"pmid": "35140242",
"host_cell": "HEK293 Flp-In embryonic kidney",
"n_rows": 1,
"n_publications": 1
}
]subcellular location uniprot
[ "Nucleus matrix (ECO:0000269)" ]
sibling preys in the same screen
[ "EN1", "NHLH1", "ELF1", "ELF2", "FEV", "KLF12", "KLF3", "MYC", "NFIX", "NFYC" ]
- YY1 is essential in most human cell lines and holds loops genome-wide; degrading it to treat a leukaemia would be an essential-function toxicity, not a targeted intervention.
- If the YY1 relationship is a looping-architecture one, it is a property of the target locus rather than of the fusion, so it would be shared with normal cells expressing the same enhancers - the therapeutic window argument has to be made before the biology is worth pursuing.
- A proximity row in an over-expression screen is exactly the kind of evidence that gets promoted into a mechanism diagram and never re-tested. If this entry is used to justify an experiment, the experiment must be able to return a clean negative.
- Does YY1 occupy the HOXA cluster, MEIS1 or any other KMT2A::AFF1 target in a KMT2A-rearranged human B-ALL line, and does YY1 depletion move their expression? A YY1 CUT&RUN in SEM plus a degron is the whole experiment.
- Is the YY1-KMT2A proximity retained for the FUSION? KMT2A::AFF1 keeps only the N-terminal third of KMT2A, so a proximity mapped to the C-terminal region would not be inherited, and BioID cannot say where on KMT2A it was.
- Of the eleven TF baits in this screen that recover KMT2A, is there any property other than abundance that separates them from the 98 that do not? That is a single analysis over the deposited table and would decide whether these eleven rows are signal or a prey-abundance artefact.
- Does the nuclear-matrix localisation of YY1 mean the proximity is a fractionation property rather than a functional one?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Goos et al. identified 6,703 BioID and 1,536 AP-MS protein-protein interactions for 109 different human transcription factors, and state that the BioID analysis identifies more high-confidence interactions, highlighting the transient and dynamic nature of many of the TF interactions.
Human transcription factor protein interaction networks. · Goos H, Kinnunen M, Salokas K, et al. · Nat Commun 2022What this evidence cannot show
Abstract read; the supplementary tables that actually contain this pair were not opened - the pair was read from the IMEx deposition IM-28767 instead. This is a 109-bait screen in a single engineered cell background (HEK293 Flp-In), so every row is an over-expressed, tagged bait in embryonic kidney cells. Rule 92 applies in reverse: an atlas-scale screen is the weakest provenance class in this graph's own audit.
Evidence that argues against this (1)
- This graph's own analysis of the same deposition records that KMT2A is recovered as prey by eleven of the 109 TF baits. A protein recovered by eleven unrelated transcription-factor baits in one screen is as consistent with a promiscuous or abundant prey as with eleven specific relationships, and the screen provides no discrimination between those readings. source 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Weintraub et al. showed that YY1 binds active enhancers and promoter-proximal elements and forms dimers that facilitate the interaction of these DNA elements, and that deletion of YY1 binding sites or depletion of YY1 protein disrupts enhancer-promoter looping and gene expression; they propose YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control.
YY1 Is a Structural Regulator of Enhancer-Promoter Loops. · Weintraub AS, Li CH, Zamudio AV, et al. · Cell 2017What this evidence cannot show
Abstract read, not full text. The work is in mouse embryonic stem cells and human cell lines, not in leukaemia and not in any KMT2A-rearranged system. Nothing in this paper concerns KMT2A; it is cited here only to establish what YY1 does, so that the proximity row can be read against a real function rather than a label.
Evidence that argues against this (1)
- The generality of YY1 looping has been contested: rapid-degradation studies of architectural proteins have repeatedly found smaller transcriptional consequences than the original depletion experiments implied. This entry does not have a specific citation in hand for a YY1 degron re-test and so records the concern rather than a refutation. source 2026
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
IntAct serves one curated human YY1-KMT2A row: MI:1314 proximity-dependent biotin identification, MI:2364 proximity, MI:1060 spoke expansion, YY1 experimental role MI:0496 bait and KMT2A MI:0498 prey, MI-score 0.27, host taxid:9606 Homo sapiens HEK293flp-in embryonic kidney cell, IMEx IM-28767, publication PMID 35140242.
IntAct molecular interaction database (EMBL-EBI), PSICQUIC tab27 record for id:P25490 AND id:Q03164 2026What this evidence cannot show
Retrieved live 2026-09-23. Rule 93: PSICQUIC is a floor relative to IntAct REST and cannot reach processed-chain identifiers, so this is a minimum row count for the pair. MI-score 0.27 is the deposition-wide value for this screen, not a pair-specific quality signal.
Evidence that argues against this (1)
- single publication, single method, spoke-expanded - the weakest interaction class this graph recognises, and flagged single_method_single_paper by this project's own instrument. source 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProt P25490 is 414 aa, records YY1 as a multifunctional transcription factor binding the consensus 5'-CCGCCATNTT-3' and as a proposed core component of the chromatin-remodelling INO80 complex, and assigns the experimental (ECO:0000269) subcellular location 'Nucleus matrix'.
What this evidence cannot show
Fetched live 2026-09-23. Rule 91: the ECO:0000269 code says a curator read an experiment in a cited paper, not that the paper is the founding or best observation; the underlying papers were not opened. The INO80 membership is recorded by UniProt as 'proposed', which is weaker than the rest of the comment.
Evidence that argues against this (1)
- UniProt records the INO80 membership as 'proposed', which is weaker than the rest of the comment and is the part of this claim a reader is most likely to over-read. The nuclear-matrix location is also an operationally defined compartment - what survives extraction - rather than a structure observed in a living cell, so it constrains fractionation behaviour more than it constrains biology. source 2026
- co-occurs with →KMT2A / MLL1 — the gene that breaks
YY1 bait / KMT2A prey, one spoke-expanded BioID row (MI:1314), IntAct IM-28767, HEK293 Flp-In - proximity, not binding
one of the eleven TF baits in this screen that recover KMT2A
- related to →Plain-English: chromatin and epigenetics — the sticky notes on the DNA, and which ones matter here
enhancer-promoter loop factor; proposed INO80 core component
- related to →Plain-English: what transcription elongation is, and why a traffic light explains this leukemia
holds the enhancer-promoter contacts across which a fusion-driven elongation programme would have to act
same deflationary control applies to the YY1 row