Leicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UK.
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UK.
Cell Rep. 2020 Feb 25;30(8):2699-2711.e8. doi: 10.1016/j.celrep.2020.01.091.
The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. The CoREST complex is unique in containing both histone demethylase and deacetylase enzymes, LSD1 and HDAC1, held together by the RCOR1 scaffold protein. To date, it has been assumed that the enzymes function independently within the complex. Now, we report the assembly of the ternary complex. Using both structural and functional studies, we show that the activity of the two enzymes is closely coupled and that the complex can exist in at least two distinct states with different kinetics. Electron microscopy of the complex reveals a bi-lobed structure with LSD1 and HDAC1 enzymes at opposite ends of the complex. The structure of CoREST in complex with a nucleosome reveals a mode of chromatin engagement that contrasts with previous models.
转录核心抑制复合物 CoREST 是通过控制染色质乙酰化来调节基因组的七个组蛋白去乙酰化酶复合物之一。CoREST 复合物的独特之处在于它同时包含组蛋白去甲基化酶和去乙酰化酶 LSD1 和 HDAC1，由 RCOR1 支架蛋白固定在一起。迄今为止，人们一直认为该复合物中的酶是独立发挥作用的。现在，我们报告了三元复合物的组装。通过结构和功能研究，我们表明两种酶的活性紧密偶联，并且该复合物至少可以存在两种具有不同动力学的不同状态。该复合物的电子显微镜显示出一种具有双叶结构的复合物，LSD1 和 HDAC1 酶位于复合物的两端。与先前的模型相比，CoREST 与核小体复合物的结构揭示了一种不同的染色质结合模式。
