Epigenome and Chromatin Structure in Human Embryonic Stem Cells Undergoing Differentiation
Epigenome and Chromatin Structure in Human Embryonic Stem Cells Undergoing Differentiation
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DOI：
10.1002/dvdy.21773
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发表时间：
2008-12-01
影响因子：
2.5
通讯作者：
Kozubek, Stanislav
中科院分区：
文献类型：
--
作者：
Bartova, Eva;Galiova, Gabriela;Kozubek, Stanislav
表观遗传组蛋白（H3）的修饰模式和选择的遗传元件的核放射状排列在人胚胎干细胞（hESCs）分化前后进行了比较。H3 K9乙酰化、H3 K9三甲基化和H3 K79单甲基化在分化的hESC的核周边减少。分化与着丝粒重新分布相吻合，证明了核仁周围的积累的着丝粒标记CENP-A和H3 K9 me 3，中央重新定位的着丝粒1，5，19，和其他着丝粒在核周边的重排。PML、RAR α基因和人染色体10、12、15、17和19的径向位置随着hESC分化而保持相对稳定。然而，女性失活H3 K27-三甲基化X染色体在分化细胞中占据了更外围的核位置。因此，多能性和分化的hESC具有异染色质结构（着丝粒和失活X染色体）和表观遗传标记（H3 K9 me 3和H3 K27 me 3）的不同核模式，而相对保守的基因密度相关的径向染色质分布已经在未分化的hES细胞中大部分建立。发展动力学237：3690-3702，2008年。(C)2008 Wiley-Liss，Inc.
Epigenetic histone (H3) modification patterns and the nuclear radial arrangement of select genetic elements were compared in human embryonic stem cells (hESCs) before and after differentiation. H3K9 acetylation, H3K9 trimethylation, and H3K79 monomethylation were reduced at the nuclear periphery of differentiated hESCs. Differentiation coincided with centromere redistribution, as evidenced by perinucleolar accumulation of the centromeric markers CENP-A and H3K9me3, central repositioning of centromeres 1, 5, 19, and rearrangement of other centromeres at the nuclear periphery. The radial positions of PML, RAR alpha genes, and human chromosomes 10, 12, 15, 17, and 19 remained relatively stable as hESCs differentiated. However, the female inactive H3K27-trimethylated X chromosome occupied a more peripheral nuclear position in differentiated cells. Thus, pluripotent and differentiated hESCs have distinct nuclear patterns of heterochromatic structures (centromeres and inactive X chromosome) and epigenetic marks (H3K9me3, and H3K27me3), while relatively conserved gene density-related radial chromatin distributions are already largely established in undifferentiated hES cells. Developmental Dynamics 237: 3690-3702, 2008. (C) 2008 Wiley-Liss, Inc.