A conserved, extended chromatin opening within α-globin locus during development
A conserved, extended chromatin opening within α-globin locus during development
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DOI：
10.1016/j.yexcr.2005.05.015
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发表时间：
2005-09-10
影响因子：
3.7
通讯作者：
Liang, CC
中科院分区：
文献类型：
--
作者：
Fu, XH;Liu, DP;Liang, CC
组蛋白修饰在真核基因调控中发挥重要作用。然而，人们对发育过程中组蛋白修饰的动态变化知之甚少。此外，组蛋白修饰和珠蛋白基因转换之间的关系仍不清楚。在这里，我们评估了体内珠蛋白基因转换期间沿小鼠α珠蛋白基因座以及转基因小鼠中沿人类α珠蛋白基因座的历史修饰（H3乙酰化、H4乙酰化、H3K4甲基化和H3K79甲基化）的动态模式。在转换过程中，胚胎 zeta 基因和胎儿/成人 α 基因的组蛋白修饰表现出不同的发育模式。 zeta 基因的历史修饰水平根据 zeta 基因表达水平进行发育调节，而 α 基因在两个发育阶段都保持高水平的组蛋白修饰，无论其表达水平如何。历史上的脱乙酰酶抑制选择性地增加了胎儿肝脏中失活的zeta基因的乙酰化，尽管它并没有重新激活基因表达。更重要的是，在转换过程中观察到主要调控元件和胎儿/成人α基因的组蛋白修饰水平明显增加，这表明在珠蛋白基因转换过程中，位点内发生了保守的、扩展的染色质开放。 (c) 2005 Elsevier Inc. 保留所有权利。
Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of historic modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine alpha-globin locus, as well as along the human alpha-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic zeta-gene and fetal/adult alpha-genes displayed different developmental patterns. The level of historic modification at zeta-gene was developmentally regulated, in accordance with the level of zeta-gene expression, whereas the alpha-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Historic deacetylase inhibition selectively increased acetylation at the inactive zeta-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult alpha-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching. (c) 2005 Elsevier Inc. All rights reserved.