Histone deacetylase activity is required for embryonic stem cell differentiation
Histone deacetylase activity is required for embryonic stem cell differentiation
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DOI：
10.1002/gene.10250
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发表时间：
2004-01-01
期刊：
影响因子：
1.5
通讯作者：
Skalnik, DG
中科院分区：
文献类型：
--
作者：
Lee, JH;Hart, SRL;Skalnik, DG
哺乳动物的发育需要细胞对限制谱系的承诺，这需要对染色质结构的表观遗传调节。在鼠胚胎干细胞的体外分化过程中，检查了表观遗传修饰。整体组蛋白乙酰化是一种构素标志物，在分化诱导的1天之内急剧下降，并在第2天之前部分反弹。在体外分化过程中，组蛋白H3-Lys9甲基化（一种异染色质标记）增加。相反，构素标记物H3-Lys4甲基化瞬时降低，然后在第4天之前增加到未分化的水平，并在第6天之前降低。在ES细胞分化过程中，全球胞质甲基化（另一种异质染色质标记物）在ES细胞分化过程中略微增加。 OCT4和Brachyury基因启动子的染色质结构与ES细胞分化过程中的表达方式一起调节。重要的是，通过用滴虫素A处理预防全球组蛋白脱乙酰基化可以防止ES细胞分化。因此，ES细胞在体外分化过程中经历功能上重要的全球和基因特异性重塑。 （c）2003 Wiley-Liss，Inc。
Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3-Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3-Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene-specific remodeling of chromatin structure during in vitro differentiation. (C) 2003 Wiley-Liss, Inc.