Silverstein Rebecca A, Ekwall Karl
Karolinska Institutet, Department of Biosciences, University College Sodertorn, Alfred Nobels Allé 7, 141 89, Huddinge, Sweden.
Curr Genet. 2005 Jan;47(1):1-17. doi: 10.1007/s00294-004-0541-5. Epub 2004 Nov 23.
SIN3 was first identified genetically as a global regulator of transcription. Sin3 is a large protein composed mainly of protein-interaction domains, whose function is to provide structural support for a heterogeneous Sin3/histone deacetylase (HDAC) complex. The core Sin3/HDAC complex is conserved from yeast to man and consists of eight proteins. In addition to HDACs, Sin3 can sequester other enzymatic functions, including nucleosome remodeling, DNA methylation, N-acetylglucoseamine transferase activity, and histone methylation. Since the Sin3/HDAC complex lacks any DNA-binding activity, it must be targeted to gene promoters by interacting with DNA-binding proteins. Although most research on Sin3 has focused on its role as a corepressor, mounting evidence suggests that Sin3 can also positively regulate transcription. Furthermore, Sin3 is key to the propagation of epigenetically silenced domains and is required for centromere function. Thus, Sin3 provides a platform to deliver multiple combinations modifications to the chromatin, using both sequence-specific and sequence-independent mechanisms.
SIN3最初是通过遗传学方法被鉴定为一种全局转录调节因子。Sin3是一种主要由蛋白质相互作用结构域组成的大型蛋白质，其功能是为异质性Sin3/组蛋白去乙酰化酶（HDAC）复合物提供结构支持。核心Sin3/HDAC复合物从酵母到人类都保守，由八种蛋白质组成。除了HDACs，Sin3还可以结合其他酶活性，包括核小体重塑、DNA甲基化、N-乙酰葡糖胺转移酶活性和组蛋白甲基化。由于Sin3/HDAC复合物缺乏任何DNA结合活性，它必须通过与DNA结合蛋白相互作用而靶向基因启动子。尽管大多数关于Sin3的研究都集中在其作为共抑制因子的作用上，但越来越多的证据表明Sin3也可以正向调节转录。此外，Sin3是表观遗传沉默结构域传播的关键，并且是着丝粒功能所必需的。因此，Sin3提供了一个平台，利用序列特异性和序列非依赖性机制对染色质进行多种组合修饰。
