Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A

Shuping Zhong, Hidemasa Goto, Masaki Inagaki, Zigang Dong

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5291-5297
Number of pages7
JournalOncogene
Volume22
Issue number34
DOIs
StatePublished - Aug 14 2003

Bibliographical note

Funding Information:
We thank Dr Ann Bode and Dr Debbie Johnson for scientific discussion and editorial advice and Andria Hansen for secretarial assistance. This work was supported by The Hormel Foundation and National Institutes of Health Grants CA77646 and CA27502.

Keywords

  • Acetylation
  • Histone H3
  • MAP kinase
  • Phosphorylation
  • Trichostatin A
  • Ultraviolet

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