Acetylation of core histones in response to HDAC inhibitors is diminished in mitotic HeLa cells.
Histone acetylation is a key modification that regulates chromatin accessibility. Here we show that treatment with butyrate or other histone deacetylase (HDAC) inhibitors does not induce histone hyperacetylation in metaphase-arrested HeLa cells. When compared to similarly treated interphase cells, acetylation levels are significantly decreased in all four core histones and at all individual sites examined. However, the extent of the decrease varies, ranging from only slight reduction at H3K23 and H4K12 to no acetylation at H3K27 and barely detectable acetylation at H4K16. Our results show that the bulk effect is not due to increased or butyrate-insensitive HDAC activity, though these factors may play a role with some individual sites. We conclude that the lack of histone acetylation during mitosis is primarily due to changes in histone acetyltransferases (HATs) or changes in chromatin. The effects of protein phosphatase inhibitors on histone acetylation in cell lysates suggest that the reduced ability of histones to become acetylated in mitotic cells depends on protein phosphorylation.
Patzlaff
Jason S
JS
Department of Chemistry, University of Wisconsin-Oshkosh, 800 Algoma Blvd, Oshkosh, WI 54901, USA. patzlaffj@gmail.com
Terrenoire
Edith
E
Turner
Bryan M
BM
Earnshaw
William C
WC
Paulson
James R
JR
D000107:Acetylation; D002087:Butyrates / Q000494:pharmacology; D002843:Chromatin / Q000502:physiology; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases
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