Cdyl, a New Partner of the Inactive X Chromosome and Potential Reader of H3K27me3 and H3K9me2
Cdyl, a New Partner of the Inactive X Chromosome and Potential Reader of H3K27me3 and H3K9me2
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DOI：
10.1128/mcb.00866-13
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发表时间：
2013-12-01
影响因子：
5.3
通讯作者：
Heard, E.
中科院分区：
文献类型：
--
作者：
Escamilla-Del-Arenal, M.;da Rocha, S. T.;Heard, E.
X染色体失活是染色体范围内基因沉默和兼性异染色质形成的一个显著例子。许多组蛋白翻译后修饰，包括H3K9me2和H3K27me3，伴随着这一过程，尽管我们对奠定这些标记的酶和与它们结合的因子的理解仍然不完整。在这里，我们确定了Cdyl，一个含染色质结构域的转录辅抑制因子，作为一个新的染色质相关蛋白伴侣的失活X染色体（Xi）。使用组蛋白甲基转移酶活性突变的小鼠胚胎干细胞系，我们发现Cdyl依赖于H3K9me2与体内染色质的一般关联。Cdyl与Xi的关联需要分化过程以及H3K9me2和H3K27me3的存在，而H3K9me2和H3K27me3在Xist RNA包被后都会在染色体上富集。我们进一步表明，去除PRC2组分Eed和随后H3K27me3的损失导致Cdyl和H3K9me2在非活性Xi上的富集减少。最后，我们发现Cdyl与H3K9组蛋白甲基转移酶G9a和MGA蛋白结合，这两种蛋白也在Xi上发现。我们提出H3K9me2和H3K27me3的结合将Cdyl招募到Xi，这反过来可能通过锚定G9a来促进H3K9me2标记的传播。
X chromosome inactivation is a remarkable example of chromosome-wide gene silencing and facultative heterochromatin formation. Numerous histone posttranslational modifications, including H3K9me2 and H3K27me3, accompany this process, although our understanding of the enzymes that lay down these marks and the factors that bind to them is still incomplete. Here we identify Cdyl, a chromodomain-containing transcriptional corepressor, as a new chromatin-associated protein partner of the inactive X chromosome (Xi). Using mouse embryonic stem cell lines with mutated histone methyltransferase activities, we show that Cdyl relies on H3K9me2 for its general association with chromatin in vivo. For its association with Xi, Cdyl requires the process of differentiation and the presence of H3K9me2 and H3K27me3, which both become chromosomally enriched following Xist RNA coating. We further show that the removal of the PRC2 component Eed and subsequent loss of H3K27me3 lead to a reduction of both Cdyl and H3K9me2 enrichment on inactive Xi. Finally, we show that Cdyl associates with the H3K9 histone methyltransferase G9a and the MGA protein, both of which are also found on Xi. We propose that the combination of H3K9me2 and H3K27me3 recruits Cdyl to Xi, and this, in turn, may facilitate propagation of the H3K9me2 mark by anchoring G9a.