Onishi Megumi, Liou Gunn-Guang, Buchberger Johannes R, Walz Thomas, Moazed Danesh
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 2007 Dec 28;28(6):1015-28. doi: 10.1016/j.molcel.2007.12.004.
Silent chromatin domains in Saccharomyces cerevisiae represent examples of epigenetically heritable chromatin. The formation of these domains involves the recruitment of the SIR complex, composed of Sir2, Sir3, and Sir4, followed by iterative cycles of NAD-dependent histone deacetylation and spreading of SIR complexes over adjacent chromatin domains. We show here that the conserved bromo-adjacent homology (BAH) domain of Sir3 is a nucleosome- and histone-tail-binding domain and that its binding to nucleosomes is regulated by residues in the N terminus of histone H4 and the globular domain of histone H3 on the exposed surface of the nucleosome. Furthermore, using a partially purified system containing nucleosomes, the three Sir proteins, and NAD, we observe the formation of SIR-nucleosome filaments with a diameter of less than 20 nm. Together, these observations suggest that the SIR complex associates with an extended chromatin fiber through interactions with two different regions in the nucleosome.
酿酒酵母中的沉默染色质结构域代表了表观遗传可遗传染色质的实例。这些结构域的形成涉及由Sir2、Sir3和Sir4组成的SIR复合物的募集,随后是依赖NAD的组蛋白去乙酰化的迭代循环以及SIR复合物在相邻染色质结构域上的扩散。我们在此表明,Sir3保守的溴相邻同源(BAH)结构域是一个核小体和组蛋白尾结合结构域,其与核小体的结合受组蛋白H4 N端残基和核小体暴露表面上组蛋白H3球状结构域的调节。此外,使用含有核小体、三种Sir蛋白和NAD的部分纯化系统,我们观察到直径小于20 nm的SIR-核小体细丝的形成。总之,这些观察结果表明,SIR复合物通过与核小体中两个不同区域的相互作用与延伸的染色质纤维结合。