Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability.
Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability.
复制标题
GLP 识别 H3K9 甲基化对于有效建立 H3K9 甲基化、快速靶基因抑制和小鼠生存能力是必需的。
DOI：
10.1101/gad.254425.114
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发表时间：
2015-02-15
影响因子：
10.5
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Liu N;Zhang Z;Wu H;Jiang Y;Meng L;Xiong J;Zhao Z;Zhou X;Li J;Li H;Zheng Y;Chen S;Cai T;Gao S;Zhu B
GLP和G9a是小鼠早期胚胎发育所必需的主要H3K9二甲基酶。在此，Liu等人报道了GLP和G9a的组蛋白甲基转移酶活性受到在H3K9处预甲基化的相邻核小体的刺激。在小鼠胚胎干细胞窝藏突变GLP，缺乏H3K9me1结合活性，关键的多能基因表现出低效的H3K9me2和延迟的基因沉默在分化过程中的建立。携带H3K9me1结合突变型GLP的小鼠显示胚胎生长迟缓和颅骨骨形成缺陷。GLP和G9a是主要的H3K9二甲基酶，对小鼠早期胚胎发育至关重要。GLP和G9a都具有能够结合H3K9甲基化的锚蛋白重复结构域。然而，它们识别H3K9甲基化的功能意义是未知的。在这里，我们报告说，GLP和G9a的组蛋白甲基转移酶活性的刺激，在H3K9的预甲基化的相邻的核小体。这些刺激事件顺式发挥作用，并且依赖于GLP和G9a的锚蛋白重复结构域的H3K9甲基化结合活性。GLP在小鼠中的H3K9甲基化结合活性的破坏导致胚胎的生长迟缓、颅骨的骨化缺陷和由于幼仔饥饿引起的出生后致死。在小鼠胚胎干细胞（ESC）中，含有缺乏H3K9me1结合活性的突变GLP，关键的多能基因，包括Oct4和Nanog，显示H3K9me2的建立效率低下，并在分化过程中延迟基因沉默。总的来说，我们的研究揭示了GLP和G9a在ESC分化和小鼠生存力中发挥重要作用的新激活机制。
GLP and G9a are major H3K9 dimethylases essential for mouse early embryonic development. Here, Liu et al. report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. In mouse embryonic stem cells harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes displayed inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Mice carrying the H3K9me1-binding mutant form of GLP displayed embryonic growth retardation and defects in calvaria bone formation. GLP and G9a are major H3K9 dimethylases and are essential for mouse early embryonic development. GLP and G9a both harbor ankyrin repeat domains that are capable of binding H3K9 methylation. However, the functional significance of their recognition of H3K9 methylation is unknown. Here, we report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. These stimulation events function in cis and are dependent on the H3K9 methylation binding activities of ankyrin repeat domains of GLP and G9a. Disruption of the H3K9 methylation-binding activity of GLP in mice causes growth retardation of embryos, ossification defects of calvaria, and postnatal lethality due to starvation of the pups. In mouse embryonic stem cells (ESCs) harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes, including Oct4 and Nanog, display inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Collectively, our study reveals a new activation mechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability.
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影响因子：
4.5
作者：
Lienert F;Mohn F;Tiwari VK;Baubec T;Roloff TC;Gaidatzis D;Stadler MB;Schübeler D
通讯作者：
Schübeler D
影响因子：
10.5
作者：
Chen, Xiaoji;Skutt-Kakaria, Kyobi;Paddison, Patrick J.
通讯作者：
Paddison, Patrick J.
影响因子：
10.5
作者：
Esteve, Pierre-Olivier;Chin, Hang Gyeong;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa
影响因子：
16.8
作者：
Collins, Robert E.;Northrop, Jeffrey P.;Cheng, Xiaodong
通讯作者：
Cheng, Xiaodong
影响因子：
7.7
作者：
Chen, Xiuzhen;Xiong, Jun;Zhu, Bing
通讯作者：
Zhu, Bing