Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3, and SIRT1

Shashi Gandhi, Raizy Mitterhoff, Rachel Rapoport, Marganit Farago, Avraham Greenberg, Lauren Hodge, Sharon Eden, Christopher Benner, Alon Goren, Itamar Simon

Research output: Contribution to journalArticlepeer-review

Abstract

Histone acetylation levels are reduced during mitosis. To study the mitotic regulation of H3K9ac, we used an array of inhibitors targeting specific histone deacetylases. We evaluated the involvement of the targeted enzymes in regulating H3K9ac during all mitotic stages by immunofluorescence and immunoblots. We identified HDAC2, HDAC3, and SIRT1 as modulators of H3K9ac mitotic levels. HDAC2 inhibition increased H3K9ac levels in prophase, whereas HDAC3 or SIRT1 inhibition increased H3K9ac levels in metaphase. Next, we performed ChIP-seq on mitotic-arrested cells following targeted inhibition of these histone deacetylases. We found that both HDAC2 and HDAC3 have a similar impact on H3K9ac, and inhibiting either of these two HDACs substantially increases the levels of this histone acetylation in promoters, enhancers, and insulators. Altogether, our results support a model in which H3K9 deacetylation is a stepwise process—at prophase, HDAC2 modulates most transcription-associated H3K9ac-marked loci, and at metaphase, HDAC3 maintains the reduced acetylation, whereas SIRT1 potentially regulates H3K9ac by impacting HAT activity.

Original languageAmerican English
Article numbere202201433
JournalLife Science Alliance
Volume5
Issue number10
DOIs
StatePublished - Oct 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology

Fingerprint

Dive into the research topics of 'Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3, and SIRT1'. Together they form a unique fingerprint.

Cite this