Activation of the mouse cytokeratin A (endo A) gene in teratocarcinoma F9 cells by the histone deacetylase inhibitor Trichostatin A.
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 endoA expression in F9 cells, and was effective 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 endoA gene expression is unknown, but these results suggest that endoA expression is induced by inhibition of histone deacetylase and that the effect is at the transcriptional level.
Miyashita
T
T
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan.
Yamamoto
H
H
Nishimune
Y
Y
Nozaki
M
M
Morita
T
T
Matsushiro
A
A
D000818:Animals; D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007633:Keratins / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013724:Teratoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D020148:Butyric Acid; C012589:trichostatin A; D007633:Keratins; D004247:DNA; D003850:Deoxyribonuclease I