dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing
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DOI：
10.1101/gad.484208
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发表时间：
2008-10-15
影响因子：
10.5
通讯作者：
Verrijzer, C. Peter
中科院分区：
文献类型：
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作者：
Lagarou, Anna;Mohd-Sarip, Adone;Verrijzer, C. Peter
转录调控涉及酶介导的染色质结构变化。在这里，我们描述了基因沉默过程中组蛋白串扰的一种新模式，其中组蛋白 H2A 单泛素化与组蛋白 H3 Lys 36 二甲基化 (H3K36me2) 的去除相结合。通过鉴定 dRING 相关因子 (dRAF)，一种新型 Polycomb 基团 (PcG) 沉默复合物，包含组蛋白 H2A 泛素连接酶 dRING、PSC 和 F-box 蛋白以及去甲基化酶 dKDM2，发现了该通路。在体内，dKDM2 与 Polycomb 共享许多转录靶点，并抵消组蛋白甲基转移酶 TRX 和 ASH1。重要的是，细胞耗竭和体外重建测定表明，dKDM2 不仅介导 H3K36me2 去甲基化，而且也是 dRING/PSC 有效 H2A 泛素化所必需的。因此，dRAF 从组蛋白 H3 中去除了一个活性标记，并向 H2A 添加了一个抑制性标记。这些发现揭示了 PcG 复合物协调跨组蛋白调节以介导基因抑制。
Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.