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: The Tip60 acetylome is a hallmark of the proliferative state in Drosophila

ABSTRACT: The acetyltransferase KAT5/Tip60 is a key epigenetic regulator of transcription and the DNA damage response. In Drosophila, Tip60 functions within the DOM-A complex to acetylate histones, but its broader substrate repertoire and cellular roles remain incompletely defined. Here, we comprehensively investigated the functions of Tip60 in a proliferative Drosophila cell model. Tip60 depletion caused cell cycle arrest, yet surviving cells exhibited resistance to mutagenic irradiation. This impaired proliferation was accompanied by reduced expression of critical cell cycle regulators, with Tip60 binding at their transcription start sites and Tip60-dependent acetylation of the histone variant H2A.V correlating with transcriptional activation. Beyond chromatin, Tip60 was found to acetylate a wide range of nuclear proteins involved in replication, mitosis, gene expression, chromatin organization, and ribosome biogenesis. These findings suggest that Tip60 coordinates the proliferative state through the combined regulation of histone and non-histone substrates. We propose that reversible acetylation of diverse effector proteins provides a mechanism for dynamically adjusting growth-related processes in response to cellular stress or nutrient availability. Collectively, this work identifies the DOM-A/Tip60 complex as a general promoter of cell proliferation.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Ignasi Forne

LAB HEAD: Prof. Dr. Peter Becker

PROVIDER: PXD066107 | Pride | 2025-07-16

REPOSITORIES: Pride

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			Action	DRS
	Acetyl_K_Sites.txt	Txt
	Ref6804_AV_IP_01_20211019.raw	Raw
	Ref6804_AV_IP_02_20211019.raw	Raw
	Ref6804_AV_IP_03_20211019.raw	Raw
	Ref6804_AV_IP_04_20211019.raw	Raw

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