Functional role of G9a-induced histone methylation in small heterodimer partner-mediated transcriptional repression
Functional role of G9a-induced histone methylation in small heterodimer partner-mediated transcriptional repression
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DOI：
10.1093/nar/gkh947
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Talianidis, I
中科院分区：
文献类型：
--
作者：
Boulias, K;Talianidis, I
核小体组蛋白的定点修饰在转录活性和非活性染色质结构的形成中起着核心作用。这些修饰可以作为染色质蛋白的特定识别基序，作为采取适当调控反应的信号。在这里，我们证明了孤儿核受体SHP(小异源二聚体伙伴)，一种抑制几个核受体活性的辅助调节因子，可以与未修饰和赖氨酸9-甲基化的组蛋白-3相关联，但不与乙酰化蛋白相关联。自然产生的SHP突变体(R213C)表现出降低的转录抑制能力，与K9甲基化的组蛋白3相互作用不那么强烈。我们证明SHP可以与组蛋白脱乙酰酶-1和G9a甲基转移酶功能相互作用，并且它只定位于核酸酶敏感的常染色质。这些结果表明，SHP依赖的转录抑制是一个多步骤的机制，包括组蛋白去乙酰化，随后是H3-K9甲基化，以及SHP本身与染色质的稳定结合。
Site-specific modification of nucleosomal histones plays a central role in the formation of transcriptionally active and inactive chromatin structures. These modifications may serve as specific recognition motifs for chromatin proteins, which act as a signal for the adoption of the appropriate regulatory responses. Here, we show that the orphan nuclear receptor SHP (small heterodimer partner), a coregulator that inhibits the activity of several nuclear receptors, can associate with unmodified and lysine 9-methylated histone-3, but not with the acetylated protein. The naturally occurring SHP mutant (R213C), which exhibits decreased transrepression potential, interacts less avidly with K9-methylated histone 3. We demonstrate that SHP can functionally interact with histone deacetylase-1 and the G9a methyltransferase and that it is localized exclusively in nuclease-sensitive euchromatin. The results point to the involvement of a multistep mechanism in SHP-dependent transcriptional repression, which includes histone deacetylation, followed by H3-K9 methylation and stable association of SHP itself with chromatin.