Kato Shigeaki, Kim Mi-sun, Yamaoka Kazuyoshi, Fujiki Ryoji
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Curr Opin Nephrol Hypertens. 2007 Jul;16(4):297-304. doi: 10.1097/MNH.0b013e3281c55f16.
Vitamin D has diverse biological actions, and consequently the mechanisms behind how it regulates gene transcription are diverse. Unlike its well described positive effects on gene transcription, little is known about how vitamin D induces transcriptional repression.
Vitamin D-induced transcriptional repression of several negative vitamin D receptor target genes has been studied on a molecular level. A new class of negative vitamin D response elements, which are E-box-type motifs, bind the bHLH-type transcriptional activator (VDIR) together with a histone acetyltransferase coactivator. The vitamin D receptor, activated by vitamin D, does not directly bind to the negative vitamin D response elements, but instead associates with VDIR. This leads to the dissociation of the histone acetyltransferase coactivator and recruitment of a histone deacetylase corepressor to transrepress transcription of the target gene promoter.
Histone inactivation induced by histone deacetylase co-repressors appears to facilitate vitamin D-induced transcriptional repression via the vitamin D receptor. Following vitamin D binding, structural alteration of the DNA-unbound vitamin D receptor triggers transcriptional repression. Given this, the mechanisms behind vitamin D-induced transcriptional repression are probably more complex than those of vitamin D-induced transactivation.
维生素D具有多种生物学作用，因此其调节基因转录的机制也多种多样。与其对基因转录的积极作用被充分描述不同，关于维生素D如何诱导转录抑制知之甚少。
已在分子水平上研究了维生素D诱导的几种负性维生素D受体靶基因的转录抑制。一类新的负性维生素D反应元件，即E盒型基序，与bHLH型转录激活因子（VDIR）以及组蛋白乙酰转移酶共激活因子结合。被维生素D激活的维生素D受体不直接与负性维生素D反应元件结合，而是与VDIR相互作用。这导致组蛋白乙酰转移酶共激活因子解离，并募集组蛋白去乙酰化酶共抑制因子以反式抑制靶基因启动子的转录。
组蛋白去乙酰化酶共抑制因子诱导的组蛋白失活似乎通过维生素D受体促进了维生素D诱导的转录抑制。维生素D结合后，未与DNA结合的维生素D受体的结构改变触发转录抑制。鉴于此，维生素D诱导的转录抑制背后的机制可能比维生素D诱导的反式激活更为复杂。
