Structural basis for specific binding of polycomb chromodomain to histone H3 methylated at Lys 27
Structural basis for specific binding of polycomb chromodomain to histone H3 methylated at Lys 27
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DOI：
10.1101/gad.269603
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发表时间：
2003-08-01
影响因子：
10.5
通讯作者：
Xu, RM
中科院分区：
文献类型：
--
作者：
Min, JR;Zhang, Y;Xu, RM
果蝇多梳蛋白的染色体结构域在果蝇发育过程中维持同卵异体基因的沉默状态是必不可少的。最近的研究表明，Polycomb介导了抑制性高阶染色质结构的组装，并通过Polycomb基团抑制复合物介导组蛋白H3的Lys 27甲基化。异染色质组装的类似机制是由HP1介导的，HP1是一种与组蛋白H3在赖氨酸9位点甲基化结合的色域蛋白。为了了解甲基-Lys 27组蛋白编码识别的分子机制，我们确定了Polycomb与Lys 27三甲基化组蛋白H3肽复合物的1.4埃分辨率结构。该结构揭示了甲基赖氨酸结合的保守模式，并确定了polycomb与组蛋白H3的特异性相互作用。该结构还揭示了晶格中的dPC二聚体，该二聚体是由Polycomb家族中特别保守的残基介导的。dPC的二聚化可以有效地解释组蛋白结合特异性，并为Polycomb的功能提供新的机制见解。我们认为自联想对Polycomb具有重要的功能。
The chromodomain of Drosophila Polycomb protein is essential for maintaining the silencing state of homeotic genes during development. Recent studies suggest that Polycomb mediates the assembly of repressive higher-order chromatin structures in conjunction with the methylation of Lys 27 of histone H3 by a Polycomb group repressor complex. A similar mechanism in heterochromatin assembly is mediated by HP1, a chromodomain protein that binds to histone H3 methylated at Lys 9. To understand the molecular mechanism of the methyl-Lys 27 histone code recognition, we have determined a 1.4-Angstrom-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide tri-methylated at Lys 27. The structure reveals a conserved mode of methyl-lysine binding and identifies Polycomb-specific interactions with histone H3. The structure also reveals a dPC dimer in the crystal lattice that is mediated by residues specifically conserved in the Polycomb family of chromodomains. The dimerization of dPC can effectively account for the histone-binding specificity and provides new mechanistic insights into the function of Polycomb. We propose that self-association is functionally important for Polycomb.