Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells.
Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells.
复制标题
DOI：
10.1038/ng.297
复制
发表时间：
2009-02
期刊：
影响因子：
30.8
通讯作者：
Feinberg, Andrew P.
中科院分区：
文献类型：
--
作者：
Wen, Bo;Wu, Hao;Shinkai, Yoichi;Irizarry, Rafael A.;Feinberg, Andrew P.
高等真核生物必须使全能基因组适应具有稳定但有限功能的特殊细胞类型。谱系限制的一种潜在机制是染色质的变化，并且已经在单个基因中观察到与分化相关的染色质变化。我们对组蛋白 H3 赖氨酸 9 二甲基化 (H3K9Me2) 进行了全基因组观察。我们发现分化的组织表现出惊人的大 K9 修饰区域（高达 4.9 Mb），这些区域在人和小鼠之间高度保守，并且具有分化特异性，在未分化的小鼠胚胎干 (ES) 细胞中仅覆盖约 4% 的基因组，而在分化的 ES 细胞中为 31%，在肝脏中为约 46%，在大脑中为约 10%。它们需要组蛋白甲基转移酶 G9a，并且与其中基因的表达呈负相关，我们将它们称为大型组织染色质 K9 修饰 (LOCK)。 LOCK在癌细胞系中大量丢失，它们可能为发育和疾病中的表型可塑性提供细胞类型遗传机制。
Higher eukaryotes must adapt a totipotent genome to specialized cell types with a stable but limited repertoire of functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine-9 dimethylation (H3K9Me2). We find that differentiated tissues exhibit surprisingly large K9-modified regions (up to 4.9 Mb), that are highly conserved between human and mouse, and differentiation-specific, covering only ~4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, ~46% in liver and ~10% in brain. They require histone methyltransferase G9a, and are inversely related to expression of genes within them, and we term them Large Organized Chromatin K9-modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.
登录
查看更多内容
影响因子：
64.8
作者：
Reddy, K. L.;Zullo, J. M.;Singh, H.
通讯作者：
Singh, H.
影响因子：
5.3
作者：
Goetze, Sandra;Mateos-Langerak, Julio;van Driel, Roel
通讯作者：
van Driel, Roel
影响因子：
64.5
作者：
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
4
作者：
Ward, CM;Barrow, K;Stern, PL
通讯作者：
Stern, PL
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas