Developmental changes in DNA methylation and covalent histone modifications of chromatin associated with the ε-, γ-, and β-globin gene promoters in Papio anubis
Developmental changes in DNA methylation and covalent histone modifications of chromatin associated with the ε-, γ-, and β-globin gene promoters in Papio anubis
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DOI：
10.1016/j.bcmd.2006.01.004
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发表时间：
2006-03-01
影响因子：
2.3
通讯作者：
DeSimone, J
中科院分区：
文献类型：
--
作者：
Lavelle, D;Vaitkus, K;DeSimone, J
狒狒是研究人类珠蛋白基因转换机制的合适和相关的动物模型。这项研究讨论了DNA甲基化和组蛋白编码在狒狒(Papio Anubis)珠蛋白基因切换中的作用。对从不同胎龄的胎儿和成人骨髓中提纯的红系细胞进行亚硫酸氢盐测序和染色质免疫沉淀研究，以分析在发育过程中epsilon、Gamma和β珠蛋白启动子DNA甲基化的变化以及Ac-H3、Ac-H4、H3-dimeK4、H3-dimeK36和H3-dimeK79与epsilon、Gamma和β-珠蛋白启动子的关联。在珠蛋白基因转换的过渡阶段，表观珠蛋白和伽马珠蛋白基因启动子DNA甲基化的变化符合甲基化的随机模型和DNA甲基化在基因沉默中的作用。在发育活性基因的启动子上观察到Ac-H3、Ac-H4和PolII的丰富，而H3-dimeK4和H3-dimeK79的分布模式表明这些修饰在当前和以前的活性启动子附近都可以找到。在沉默的E-珠蛋白基因启动子上观察到H3-dimeK36的浓缩。这些研究表明，在发育过程中，β样珠蛋白基因启动子染色质结构的协调表观遗传修饰伴随着这些基因表达模式的高度调控变化。(C)2006 Elsevier Inc.保留所有权利。
The baboon is a suitable and relevant animal model to study the mechanism of human globin gene switching. This investigation addresses the role of DNA methylation and histone coding in globin gene switching in the baboon, Papio anubis. Bisulfite sequencing and chromatin immunoprecipitation studies were performed in erythroid cells purified from fetuses of varying gestational ages and from adult bone marrow to analyze the manner that changes in DNA methylation of the epsilon-, gamma-, and beta-globin promoters and association of ac-H3, ac-H4, H3-dimeK4, H3-dimeK36, and H3-dimeK79 with the epsilon-, gamma-, and beta-globin promoters occur during development. Changes in DNA methylation of the epsilon- and gamma-globin gene promoters during transitional stages of globin gene switching were consistent with the stochastic model of methylation and a role of DNA methylation in gene silencing. Enrichment of ac-H3, ac-H4, and pol II at the promoters of developmentally active genes was observed, while the pattern of distribution of H3-dimeK4 and H3-dimeK79 suggests that these modifications are found near both currently and formerly active promoters. Enrichment of H3-dimeK36 at the silenced E-globin gene promoter was observed. These studies demonstrate that coordinated epigenetic modifications in the chromatin structure of the beta-like globin gene promoters accompany the highly regulated changes in expression patterns of these genes during development. (c) 2006 Elsevier Inc. All rights reserved.