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

Oncogene volume 22, pages 5291–5297 (2003)Cite this article

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.

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Abbreviations

TSA:

trichostatin A

HATs:

histone acetyltransferases

HDACs:

histone deacetylases

IE:

immediate-early

EGF:

epidermal growth factor

PMSF:

phenylmethylsulfonyl fluoride

AP:

alkaline phosphatase

FBS:

fetal bovine serum

MEM:

minimal Eagle's essential medium

PVDF:

polyvinylidene difluoride

PBS:

phosphate-buffered saline

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Acknowledgements

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.

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Author notes

  1. Shuping Zhong

    Present address: School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA

Authors and Affiliations

  1. The Hormel Institute, University of Minnesota, 801, 16th Avenue NE, Austin, 55912, MN, USA

    Shuping Zhong & Zigang Dong

  2. The Laboratory of Biochemistry, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Aichi, 464-8681, Japan

    Hidemasa Goto & Masaki Inagaki

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  1. Shuping Zhong
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  2. Hidemasa Goto
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Correspondence to Zigang Dong.

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Zhong, S., Goto, H., Inagaki, M. et al. Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A. Oncogene 22, 5291–5297 (2003). https://doi.org/10.1038/sj.onc.1206507

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