Min Jinrong, Zhang Yi, Xu Rui-Ming
W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Genes Dev. 2003 Aug 1;17(15):1823-8. doi: 10.1101/gad.269603.
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-A-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide trimethylated 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.
果蝇多梳蛋白的染色质结构域对于在发育过程中维持同源异型基因的沉默状态至关重要。最近的研究表明，多梳蛋白与多梳家族阻遏复合物共同介导抑制性高阶染色质结构的组装，同时伴随着组蛋白H3赖氨酸27位的甲基化。异染色质组装中的类似机制由HP1介导，HP1是一种染色质结构域蛋白，可与赖氨酸9位甲基化的组蛋白H3结合。为了理解甲基化赖氨酸27组蛋白编码识别的分子机制，我们确定了多梳蛋白染色质结构域与赖氨酸27位三甲基化的组蛋白H3肽复合物的1.4埃分辨率结构。该结构揭示了甲基化赖氨酸结合的保守模式，并确定了多梳蛋白与组蛋白H3的特异性相互作用。该结构还揭示了晶格中的dPC二聚体，它由染色质结构域多梳家族中特异性保守的残基介导。dPC的二聚化可以有效地解释组蛋白结合特异性，并为多梳蛋白的功能提供新的机制见解。我们提出，自我缔合对多梳蛋白在功能上很重要。
