The Nuclear Localization of ACLY Guards Early Embryo Development Through Recruiting P300 and HAT1 to Promote Histone Acetylation and Transcription.

ABSTRACT: Metabolic processes and epigenetic reprogramming are intricately interconnected; however, their mechanistic interplay remains unclear. This study elucidates the role of ATP-citrate lyase (ACLY), an essential enzyme in acetyl-CoA production that uniquely localizes to the nucleus in oocytes and early embryos. Maternal Acly deletion in oocytes preserves fertility due to the compensatory upregulation of Acetyl-CoA Synthetase 2 (ACSS2), whereas zygotic Acly knockout causes developmental arrest at the pre-blastocyst stage without ACSS2 induction. Mechanistically, nuclear ACLY recruits and interacts with histone acetyltransferases, specifically E1A binding protein p300 (P300) and histone acetyltransferase 1 (HAT1), supplying acetyl-CoA for histone acetylation to activate transcription, which is e

SUBMITTER: Ma Y 

PROVIDER: S-EPMC12376542 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature