The polycomb group protein SUZ12 regulates histone h3 lysine 9 methylation and HP1α distribution
The polycomb group protein SUZ12 regulates histone h3 lysine 9 methylation and HP1α distribution
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DOI：
10.1007/s10577-007-1126-1
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发表时间：
2007-04-01
影响因子：
2.6
通讯作者：
Panning, Barbara
中科院分区：
文献类型：
--
作者：
de la Cruz, Cecile C.;Kirmizis, Antonis;Panning, Barbara
组蛋白甲基化的调节对于正确的基因表达和染色体功能至关重要。SUZ12是EED/EZH2组蛋白甲基转移酶复合物的必需成员，并且是这些复合物在体外完全活性所必需的。在哺乳动物和果蝇中，SUZ 12/Su（z）12是兼性异染色质上赖氨酸27（H3K27me3）上的组蛋白H3的三甲基化所必需的。然而，Su（z）12在多梳组蛋白中是独特的，因为Su（z）12突变体果蝇在位置效应杂色中表现出明显缺陷，表明Su（z）12在组成性异染色质形成中的作用。我们研究了Suz12在组成型异染色质中的作用，发现Suz12是分化但未分化小鼠胚胎干细胞中组蛋白H3赖氨酸9三甲基化（H3K9me3）所需的。在人类细胞中SUZ12的敲低导致H3K27me3和H3K9me3的减少，并改变了HP1 α的分布。相比之下，EZH2敲除会导致H3 K27 me3的丢失，但不会导致H3 K9 me3的丢失，这表明SUZ 12以不依赖于EZH2的方式调节H3-K9甲基化。这项工作揭示了SUZ12在H3-K9甲基化中的作用。
Regulation of histone methylation is critical for proper gene expression and chromosome function. Suppressor of Zeste 12 (SUZ12) is a requisite member of the EED/EZH2 histone methyltransferase complexes, and is required for full activity of these complexes in vitro. In mammals and flies, SUZ12/Su(z)12 is necessary for trimethylation of histone H3 on lysine 27 (H3K27me3) on facultative heterochromatin. However, Su(z)12 is unique among Polycomb Group Proteins in that Su(z)12 mutant flies exhibit gross defects in position effect variegation, suggesting a role for Su(z)12 in constitutive heterochromatin formation. We investigated the role of Suz12 in constitutive heterochromatin and discovered that Suz12 is required for histone H3 lysine 9 tri-methylation (H3K9me3) in differentiated but not undifferentiated mouse embryonic stem cells. Knockdown of SUZ12 in human cells caused a reduction in H3K27me3 and H3K9me3, and altered the distribution of HP1 alpha. In contrast, EZH2 knockdown caused loss of H3K27me3 but not H3K9me3, indicating that SUZ12 regulates H3-K9 methylation in an EZH2-independent fashion. This work uncovers a role for SUZ12 in H3-K9 methylation.