Lee Jeong-Heon, Hart Suzanne R L, Skalnik David G
Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Department of Pediatrics and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Genesis. 2004 Jan;38(1):32-8. doi: 10.1002/gene.10250.
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. genesis 38:32-38, 2004.
哺乳动物的发育需要细胞定向分化为特定谱系，这需要对染色质结构进行表观遗传调控。在小鼠胚胎干细胞（ES细胞）的体外分化过程中对表观遗传修饰进行了研究。作为常染色质标记的整体组蛋白乙酰化在分化诱导1天内急剧下降，并在第2天部分反弹。作为异染色质标记的组蛋白H3-赖氨酸9甲基化在体外分化过程中增加。相反，常染色质标记H3-赖氨酸4甲基化短暂下降，然后在第4天增加到未分化水平，并在第6天下降。另一个异染色质标记整体胞嘧啶甲基化在ES细胞分化过程中略有增加。Oct4和Brachyury基因启动子的染色质结构在ES细胞分化过程中与其表达模式协同调节。重要的是，用曲古抑菌素A处理来防止整体组蛋白去乙酰化可阻止ES细胞分化。因此，ES细胞在体外分化过程中经历了功能上重要的整体和基因特异性染色质结构重塑。《发生学》38:32 - 38，2004年。
