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

Apostolou, Zivkos; Venkatasubramani, Anuroop V.; Kopp, Lara C.; Kars, Gizem; Scacchetti, Alessandro; Campos-Sparr, Aline; Schauer, Tamas; Imhof, Axel ; Becker, Peter B. (2025): The Tip60 acetylome is a hallmark of the proliferative state in Drosophila. Nucleic Acids Research, 53 (20): gkaf1087. ISSN 0305-1048

Abstract

The acetyltransferase KAT5/Tip60 is an epigenetic regulator of transcription and the DNA damage response. In Drosophila , Tip60 acetylates hi- stones as part of the D OM-A comple x, but it is unclear whether it has other substrates. In this w ork, w e comprehensiv ely studied the functions of Tip60 in a Drosophila proliferative cell model. Depletion of Tip60 slo ws cell-cy cle progression, but remaining viable cells resist mutagenic irradiation. The impaired proliferation is explained by reduced expression of critical cell-cycle genes. Tip60 binds their transcription start sites and Tip60-dependent acetylation of the histone variant H2A.V correlates with transcription activity. A potentially synergistic pathw a y f or cell-cy cle regulation in v olv es the acetylation of proteins other than histones. T he Tip60-dependent nuclear acet ylome cont ains hundreds of proteins, many of which are in v olv ed in diverse aspects of cell growth and division, including replication, mitosis, gene expression, chromatin organization, and ribosome biogenesis. We h ypothesiz e that Tip60 coordinates the proliferative state through histone and non-histone effectors. R e v ersible acety - lation of diverse effector proteins bears potential for fine-tuning energy -intensiv e processes in response to stresses or nutritional shortcomings. Our study portra y s the DOM-A/TIP60 complex as a general promoter of cell proliferation.

• Dokumententyp: Artikel (LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Biomedizinisches Zentrum; 07 Medizin > Adolf-Butenandt-Institut
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 213249687
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892