Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells
Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells
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DOI：
10.1101/gr.084947.108
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发表时间：
2009-03-01
期刊：
影响因子：
7
通讯作者：
Choo, K. H. Andy
中科院分区：
文献类型：
--
作者：
Wong, Lee H.;Ren, Hua;Choo, K. H. Andy
目前对胚胎干细胞端粒染色质动力学的了解甚少。在这里，我们证明了在多能小鼠胚胎干细胞中，组蛋白H3.3定位于间期端粒，ser31磷酸化的H3.3富集于中期端粒。分化后端粒H3.3S31P信号降低，同时异染色质抑制标记关联增加，端粒微球菌核酸酶敏感性降低。H3.3在S/G2期晚期被募集到端粒，与端粒复制和加工一致。rnai缺失H3.3诱导端粒功能障碍表型，为H3.3在ES细胞端粒染色质完整性调控中的作用提供了证据。H3.3分布的显著变化表明，胚胎干细胞中存在一种独特且功能必需的端粒染色质，在分化过程中经历动态分化依赖性重构。
Little is known about the telomere chromatin dynamics of embryonic stem (ES) cell. Here, we demonstrate localization of histone H3.3 at interphase telomeres and enrichment of Ser31-phosphorylated H3.3 at metaphase telomeres in pluripotent mouse ES cells. Upon differentiation, telomeric H3.3S31P signal decreases, accompanied by increased association of heterochromatin repressive marks and decreased micrococcal nuclease sensitivity at the telomeres. H3.3 is recruited to the telomeres at late S/G2 phase, coinciding with telomere replication and processing. RNAi-depletion of H3.3 induces telomere-dysfunction phenotype, providing evidence for a role of H3.3 in the regulation of telomere chromatin integrity in ES cells. The distinctive changes in H3.3 distribution suggests the existence of a unique and functionally essential telomere chromatin in ES cells that undergoes dynamic differentiation-dependent remodeling during the process of differentiation.