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Functions of TIP60/NuA4 Complex Subunits in Epigenetic Regulation of Cell Differentiation

2025· preprint· en· W4414089355 on OpenAlexfundno aff
Fatemeh Hashemi, Mojtaba Shaban Loushab, Karl Riabowol

Bibliographic record

VenuePreprints.org · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMechanisms of cancer metastasis
Canadian institutionsnot available
FundersCanadian Institutes of Health Research
KeywordsChromatinEpigeneticsH3K4me3HistoneChromatin remodelingCell fate determinationTranscriptional regulationCellular differentiationEpigenetic regulation of neurogenesisHistone code

Abstract

fetched live from OpenAlex

The TIP60/NuA4 complex is a very large multifunctional histone acetyltransferase complex of >1.7 megadaltons consisting of 17-20 subunits that plays a pivotal role in epigenetic regulation of numerous cellular processes. It is targeted to the histone H3K4Me3 mark of active transcription by the ING3 epigenetic reader to alter local chromatin structure and transcription. This results in functions as a transcriptional co-activator, a histone dimer exchange factor, cell cycle and apoptosis regulator. In this study we review the effects of altering TIP60 subunit levels or mutational status on chromatin structure and transcriptional activity, and how this impacts different pathways of differentiation across multiple cell types. We focus on the molecular mechanisms by which TIP60/NuA4 contributes to cell fate decisions, focusing on its roles in histone H3 and H4 acetylation by its KAT5 catalytic subunit, chromatin remodeling, and coordination with transcription factors. We also highlight roles of individual TIP60 complex subunits with demonstrated involvement in several forms of differentiation, examining how their distinct functions contribute to lineage specification and developmental transitions. By integrating mechanistic insights with functional outcomes, this review summarizes pathways affected by the TIP60/NuA4 regulator of cellular differentiation and provides perspectives on its potential as a target for modulating cell fate in regenerative medicine.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.280
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.091
GPT teacher head0.326
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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Same venuePreprints.orgSame topicMechanisms of cancer metastasisFrench-language works237,207