Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A.
Trichostatin A (TSA), a histone deacetylase inhibitor, strongly increases acetylation of the N-terminal tails of histone H3. Many studies have correlated the function of TSA with the hyperacetylation of histone. Although histone H3 is known to be phosphorylated, the effect of acetylation on phosphorylation is not known. Here, we report that in JB6 cells, TSA induces both acetylation at lysine 9 and phosphorylation at serine 28 of histone H3. UVB irradiation, which is known to induce phosphorylation at serine 28, did not significantly affect phosphorylation of histone H3 in TSA-pretreated JB6 cells. In contrast, TSA markedly increased phosphorylation and acetylation of histone H3 in UVB-pretreated JB6 cells. TSA strongly activated MAP kinases. Moreover, PD98059 and SB202190 inhibited TSA-induced phosphorylation but not acetylation of histone H3. Dominant negative mutant ERK2 and dominant negative mutant p38 kinase blocked TSA-stimulated phosphorylation of histone H3 at serine 28. The results indicate that TSA-induced phosphorylation of histone H3 at serine 28 occurs through activation of the MAP kinase pathway and phosphorylated histone H3 is more sensitive to TSA-induced hyperacetylation. The facilitation of phosphorylation and acetylation of histone H3 induced by TSA may play a critical regulatory role in chromatin remodeling and gene expression.
Zhong
Shuping
S
The Hormel Institute, University of Minnesota, 801, 16th Avenue NE, Austin, MN 55912, USA.
Goto
Hidemasa
H
Inagaki
Masaki
M
Dong
Zigang
Z
D000107:Acetylation; D000123:Acetyltransferases / Q000187:drug effects*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D010766:Phosphorylation; D010770:Phosphotransferases / Q000187:drug effects*; D012694:Serine / Q000378:metabolism
D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D012694:Serine; D000123:Acetyltransferases; D010770:Phosphotransferases; D020928:Mitogen-Activated Protein Kinases; D008239:Lysine