Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Cell. 2013 Sep 12;154(6):1246-56. doi: 10.1016/j.cell.2013.08.043.
SWR-C/SWR1 and INO80 are multisubunit complexes that catalyze the deposition and removal, respectively, of histone variant H2A.Z from the first nucleosome at the start of genes. How they target and engage these +1 nucleosomes is unclear. Using ChIP-exo, we identified the subnucleosomal placement of 20 of their subunits across the yeast genome. The Swc2 subunit of SWR-C bound a narrowly defined region in the adjacent nucleosome-free region (NFR), where it positioned the Swr1 subunit over one of two sites of H2A.Z deposition at +1. The genomic binding maps suggest that many subunits have a rather plastic organization that allows subunits to exchange between the two complexes. One outcome of promoting H2A/H2A.Z exchange was an enhanced turnover of entire nucleosomes, thereby creating dynamic chromatin at the start of genes. Our findings provide unifying concepts on how these two opposing chromatin remodeling complexes function selectively at the +1 nucleosome of nearly all genes.
SWR-C/SWR1 和 INO80 是多亚基复合物，分别催化组蛋白变体 H2A.Z 从基因起始处第一个核小体的沉积和去除。它们如何靶向和结合这些+1 核小体尚不清楚。使用 ChIP-exo，我们在酵母基因组中鉴定了它们的 20 个亚基的亚核小体位置。SWR-C 的 Swc2 亚基结合在相邻无核小体区域 (NFR) 中一个定义狭窄的区域，在该区域中，Swr1 亚基将 H2A.Z 沉积在+1 的两个位点之一上。基因组结合图谱表明，许多亚基具有相当灵活的组织，允许亚基在两个复合物之间交换。促进 H2A/H2A.Z 交换的一个结果是整个核小体的周转率增加，从而在基因起始处产生动态染色质。我们的发现提供了统一的概念，说明这两种相反的染色质重塑复合物如何在几乎所有基因的+1 核小体上选择性地发挥作用。
