Flanagan John F, Mi Li-Zhi, Chruszcz Maksymilian, Cymborowski Marcin, Clines Katrina L, Kim Youngchang, Minor Wladek, Rastinejad Fraydoon, Khorasanizadeh Sepideh
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Nature. 2005 Dec 22;438(7071):1181-5. doi: 10.1038/nature04290.
Chromodomains are modules implicated in the recognition of lysine-methylated histone tails and nucleic acids. CHD (for chromo-ATPase/helicase-DNA-binding) proteins regulate ATP-dependent nucleosome assembly and mobilization through their conserved double chromodomains and SWI2/SNF2 helicase/ATPase domain. The Drosophila CHD1 localizes to the interbands and puffs of the polytene chromosomes, which are classic sites of transcriptional activity. Other CHD isoforms (CHD3/4 or Mi-2) are important for nucleosome remodelling in histone deacetylase complexes. Deletion of chromodomains impairs nucleosome binding and remodelling by CHD proteins. Here we describe the structure of the tandem arrangement of the human CHD1 chromodomains, and its interactions with histone tails. Unlike HP1 and Polycomb proteins that use single chromodomains to bind to their respective methylated histone H3 tails, the two chromodomains of CHD1 cooperate to interact with one methylated H3 tail. We show that the human CHD1 double chromodomains target the lysine 4-methylated histone H3 tail (H3K4me), a hallmark of active chromatin. Methylammonium recognition involves two aromatic residues, not the three-residue aromatic cage used by chromodomains of HP1 and Polycomb proteins. Furthermore, unique inserts within chromodomain 1 of CHD1 block the expected site of H3 tail binding seen in HP1 and Polycomb, instead directing H3 binding to a groove at the inter-chromodomain junction.
染色质结构域是与赖氨酸甲基化组蛋白尾巴和核酸识别相关的模块。CHD（染色质ATP酶/解旋酶-DNA结合）蛋白通过其保守的双染色质结构域和SWI2/SNF2解旋酶/ATP酶结构域调节ATP依赖的核小体组装和移动。果蝇CHD1定位于多线染色体的间带和胀泡，这些是转录活性的经典位点。其他CHD异构体（CHD3/4或Mi-2）对组蛋白去乙酰化酶复合物中的核小体重塑很重要。染色质结构域的缺失会损害CHD蛋白的核小体结合和重塑。在这里，我们描述了人类CHD1染色质结构域的串联排列结构及其与组蛋白尾巴的相互作用。与使用单个染色质结构域结合各自甲基化组蛋白H3尾巴的HP1和多梳蛋白不同，CHD1的两个染色质结构域协同作用与一个甲基化H3尾巴相互作用。我们表明，人类CHD1双染色质结构域靶向赖氨酸4-甲基化组蛋白H3尾巴（H3K4me），这是活性染色质的一个标志。甲基铵识别涉及两个芳香族残基，而不是HP1和多梳蛋白的染色质结构域所使用的三残基芳香笼。此外，CHD1染色质结构域1内的独特插入片段阻断了HP1和多梳蛋白中所见的H3尾巴结合预期位点，而是将H3结合导向染色质结构域间连接处的一个凹槽。
