RT Journal Article
SR Electronic
T1 Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3, and SIRT1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201433
DO 10.26508/lsa.202201433
VO 5
IS 10
A1 Gandhi, Shashi
A1 Mitterhoff, Raizy
A1 Rapoport, Rachel
A1 Farago, Marganit
A1 Greenberg, Avraham
A1 Hodge, Lauren
A1 Eden, Sharon
A1 Benner, Christopher
A1 Goren, Alon
A1 Simon, Itamar
YR 2022
UL http://www.life-science-alliance.org/content/5/10/e202201433.abstract
AB 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.