Effects of histone deacetylase inhibitors on transcription promoter activities of bidirectional gene pairs

Ikeda, S., Miki, M., Matsumoto, Y. and Seki, Y.

Gene pairs with a head-to-head configuration are frequently present in mammalian genomes. This arrangement of the gene pairs implies a coordinate regulation of the genes by a bidirectional promoter. In this study, we examined the effect of chromatin remodeling by histone acetylation and deacetylation on the regulation of transcription of the bidirectional gene pairs. An increase in the acetylation level of the histone protein by inhibition of histone deacetylase (HDAC) induced an open chromatin conformation in cells. Promoter activities of the bidirectional gene pairs including Apex/Osgep, Nthl1/Tsc2, and Fen1/1810006K21Rik genes were measured by a luciferase assay in the presence or absence of HDAC inhibitors. Three kinds of HDAC inhibitors, trichostatin A (TS-A), MS-275, and sirtinol, with a different target spectrum were administered to one human and 6 mouse cell lines. Although the supercoiled form of reporter plasmid demonstrated extremely high activity compared to the linear form of the same DNA in the luciferase assay, transcriptions from both supercoil and linear forms were activated to the same extent by TS-A. In many cell lines the promoter activity of the bidirectional genes was strongly activated by the addition of TS-A and MS-275. Transcription of each gene in bidirectional pairs was individually regulated by these HDAC inhibitors depending on the cell type. Sirtinol did not activate the transcription of any genes.

The Bulletin of Okayama University of Science

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