Pinskaya Marina, Nair Anitha, Clynes David, Morillon Antonin, Mellor Jane
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, United Kingdom.
Mol Cell Biol. 2009 May;29(9):2419-30. doi: 10.1128/MCB.01050-08. Epub 2009 Mar 9.
The SANT domain is a nucleosome recognition module found in transcriptional regulatory proteins, including chromatin-modifying enzymes. It shows high functional degeneracy between species, varying in sequence and copy number. Here, we investigate functions in vivo associated with two SANT motifs, SANT and SLIDE, in the Saccharomyces cerevisiae Isw1 chromatin-remodeling ATPase. We show that differences in the primary structures of the SANT and SLIDE domains in yeast and Drosophila melanogaster reflect their different functions. In yeast, the SLIDE domain is required for histone interactions, while this is a function of the SANT domain in flies. In yeast, both motifs are required for optimal association with chromatin and for formation of the Isw1b complex (Isw1, Ioc2, and Ioc4). Moreover, nucleosome remodeling at the MET16 locus is defective in strains lacking the SANT or SLIDE domain. In contrast, the SANT domain is dispensable for the interaction between Isw1 and Ioc3 in the Isw1a complex. We show that, although defective in nucleosome remodeling, Isw1 lacking the SANT domain is able to repress transcription initiation at the MET16 promoter. Thus, chromatin remodeling and transcriptional repression are distinct activities of Isw1.
SANT结构域是一种在转录调节蛋白（包括染色质修饰酶）中发现的核小体识别模块。它在不同物种间表现出高度的功能简并性，在序列和拷贝数上存在差异。在这里，我们研究了酿酒酵母Isw1染色质重塑ATP酶中与两个SANT基序（SANT和SLIDE）相关的体内功能。我们表明，酵母和黑腹果蝇中SANT和SLIDE结构域一级结构的差异反映了它们不同的功能。在酵母中，SLIDE结构域是组蛋白相互作用所必需的，而在果蝇中这是SANT结构域的功能。在酵母中，两个基序对于与染色质的最佳结合以及Isw1b复合物（Isw1、Ioc2和Ioc4）的形成都是必需的。此外，在缺乏SANT或SLIDE结构域的菌株中，MET16位点的核小体重塑存在缺陷。相比之下，SANT结构域对于Isw1a复合物中Isw1和Ioc3之间的相互作用是可有可无的。我们表明，尽管缺乏SANT结构域的Isw1在核小体重塑方面存在缺陷，但它能够抑制MET16启动子处的转录起始。因此，染色质重塑和转录抑制是Isw1的不同活性。
