Thompson Catherine C
Wyeth Research, Collegeville, Pennsylvania, USA.
Nucl Recept Signal. 2009 Dec 31;7:e010. doi: 10.1621/nrs.07010.
The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.
核受体的活性受到众多共调节因子的调控。共抑制因子既可以介导核受体抑制转录的能力，也可以抑制核受体的反式激活作用。随着我们对转录抑制机制了解得越来越多，核受体介导的抑制作用在发育和疾病中的重要性已变得清晰。哺乳动物无毛（Hr）基因编码的蛋白质因其与成熟的共抑制因子N-CoR和SMRT功能相似而被证明是一种共抑制因子。Hr基因的突变会导致小鼠和人类出现先天性脱发。对无毛蛋白在体外和体内小鼠模型中的功能研究表明，它在通过调节上皮干细胞分化来维持皮肤和毛发方面起着关键作用，并且在通过染色质重塑调节基因表达方面可能也发挥作用。
