Hassan A H, Neely K E, Vignali M, Reese J C, Workman J L
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Front Biosci. 2001 Sep 1;6:D1054-64. doi: 10.2741/hassan.
The action of multi-subunit complexes that are able to overcome the repressive effects of chromatin is an important step in the regulation of eukaryotic gene expression. Identification of complexes that modify the structure of chromatin to help factors access the underlying DNA has enhanced our understanding of how some genes are controlled. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) represent one group of complexes that regulate the level of acetylation on the N-terminal tails of core histone proteins. The SWI/SNF complex is the prototype of a second group of complexes, which use the energy of ATP-hydrolysis to alter histone-DNA contacts, leading to changes in chromatin conformation. Genetic studies in yeast have revealed that some of these multi-subunit complexes interact in vivo to control transcription of a subset of genes. It has become apparent that some gene promoters require modifications by both types of complexes. An important question regarding these two types of complexes is how they are recruited to the promoters of genes that are dependent on their activity for their expression. This review will tie together many studies on promoter recruitment of both HATs and SWI/SNF. Emphasis will be placed on recent data that demonstrates functional interplay between these two types of chromatin-remodeling activities. In addition, this review summarizes recent data demonstrating the ability of repressors and corepressors to recruit histone deacetylase complexes. Interestingly, many subunits of chromatin-modifying complexes in humans have been implicated in the development of cancer. Thus, studying how these complexes work can help us better understand human diseases.
能够克服染色质抑制作用的多亚基复合物的作用是真核基因表达调控中的重要一步。鉴定能够修饰染色质结构以帮助因子接触其下DNA的复合物,增强了我们对某些基因如何被调控的理解。组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)代表了一组调控核心组蛋白N端尾巴乙酰化水平的复合物。SWI/SNF复合物是另一组复合物的原型,它利用ATP水解的能量改变组蛋白与DNA的接触,导致染色质构象变化。酵母中的遗传学研究表明,这些多亚基复合物中的一些在体内相互作用以控制一部分基因的转录。很明显,一些基因启动子需要这两种复合物的修饰。关于这两种复合物的一个重要问题是它们如何被招募到那些依赖其活性进行表达的基因的启动子上。本综述将把许多关于HATs和SWI/SNF在启动子招募方面的研究联系起来。重点将放在最近的数据上,这些数据证明了这两种染色质重塑活性之间的功能相互作用。此外,本综述总结了最近的数据,这些数据证明了阻遏物和共阻遏物招募组蛋白去乙酰化酶复合物的能力。有趣的是,人类染色质修饰复合物的许多亚基与癌症的发生有关。因此,研究这些复合物如何工作有助于我们更好地理解人类疾病。