Activation of the mouse cytokeratin A (endo A) gene in teratocarcinoma F9 cells by the histone deacetylase inhibitor Trichostatin A

FEBS Letters

Nishimune, Yoshitake²  Matsushiro, Aizo¹  Miyashita, Tomoyuki¹  Morita, Takashi²  Nozaki, Masami²  Yamamoto, Hideyuki² 

[1]Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama, 649-64, Japan

[2]Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan

关键词: endo A;    Trichostatin A;    F9;    Histone acetylation;    Chromatin;    DNase I-hypersensitive site;   

DOI  :  10.1016/0014-5793(94)01034-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Treatment of cultured cells with sodium butyrate, that is the histone deacetylase inhibitor, induces the histone hyperacetylation and the expressions of various mammalian genes without affecting the level of protein synthesis. However, butyrate is a non-specific inhibitor of deacetylase because of its effects on various other enzymes and nuclear proteins other than histones. On the other hand, Trichostatin A (TSA) was recently found to be a potent and specific inhibitor of histone deacetylase. We examined the effect of TSA on the expression of mouse cytokeratin A (endo A). TSA increased endo A expression in F9 cells, and was efffective at a much lower concentration than sodium butyrate. We also examined the changes of chromatin structure induced by the two drugs by a DNase I-hypersensitivity assay. Both drugs induced the formation of a DNase I-hypersensitive site (DH site) in only the promoter region. The precise mechanism(s) by which the two drugs increase endo A gene expression is unknown, but these results suggest that endo A expression is induced by inhibition of histone deacetylase and that the effect is at the transcriptional level.

【 授权许可】

Unknown