脂溶性ビタミン類による遺伝子発現制御の分子機構に関する研究

概要

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Fat-soluble vitamins A and D are essential for many biological processes in a wide variety of cell types. These actions are exerted by their cognate nuclear receptors (NRs), vitamin A receptor (RAR) and vitamin D receptor (VDR), respectively. Although the molecular basis of NR-mediated transcription has been established, the regulations of the spatiotemporal target genes are not well known. Recently, we have identified the novel co-regulator complexes responsible for NR-mediated transcription. And, we also found that most of them were involved in chromatin reorganization on the promoters. Herein, I report the molecular mechanisms of cell-specific chromatin remodeling in the VDR-mediated transrepression of 25-hydroxyvitamin D_3-1α-hydroxylase [1α(OH)ase] by WSTF, an ATP-dependent chromatin remodeling factor, and RAR-mediated epigenetic regulation through O-linked N-acetylglucosamin signaling during HL60 differentiation. These studies would help our understanding a basic mechanism how tissue-specific regulations of NR target genes were achieved.
2012-03-25