Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice
Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice
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DOI：
10.1016/j.ydbio.2004.11.025
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发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Matsui, Y
中科院分区：
文献类型：
--
作者：
Seki, Y;Hayashi, K;Matsui, Y
小鼠生殖细胞的诱导发生在胚胎日左右的近端外胚层(E) 7.0。这些生殖细胞然后迁移到，并在大约E10.5进入性腺，之后它们经历表观遗传重编程，包括消除亲代印记。然而，新生生殖细胞获得的表观遗传特性以及这些表观遗传标记在随后的迁移期间的潜在重塑在很大程度上尚未被探索。在这里，我们使用免疫组织化学检查了发生在生殖细胞中的几种全基因组表观遗传修饰，从它们的规格到它们在生殖器脊上的定植。我们发现，在E8.0左右，生殖细胞同时显著降低了H3-K9二甲基化和DNA甲基化，这是基因表达的两个主要抑制修饰。在这些事件发生之前，所有的DNA甲基转移酶从细胞核中暂时丧失。相比之下，生殖细胞在E8.5-9.0时显著增加H3-K27三甲基化（另一种更具可塑性的抑制性修饰）的水平，并保持这种状态至少到E12.5。H3-K4甲基化和H3-K9乙酰化，与转录许可/活性染色质相关的修饰，在生殖细胞和周围体细胞中是相似的，但生殖细胞在进入生殖嵴后会短暂地急剧增加这些标记。H3-K9三甲基化是着丝异染色质的标志，在研究期间保持相对恒定。我们认为，在前迁移和迁移生殖细胞中，这种有序和广泛的表观遗传重编程可能是它们重新获得潜在的全能性、随后的特异性表观遗传重塑（包括亲本印记的重置）和产生具有适当表观遗传型的配子以支持正常发育所必需的。(C) 2004爱思唯尔公司版权所有。
Induction of mouse germ cells occurs from the proximal epiblast at around embryonic day (E) 7.0. These germ cells then migrate to, and enter the gonads at about E10.5 after which they undergo epigenetic reprogramming including erasure of parental imprints. However, the epigenetic properties acquired by nascent germ cells and the potential remodeling of these epigenetic marks in the subsequent migratory period have been largely unexplored. Here we have used immunohistochemistry to examine several genome-wide epigenetic modifications occurring in germ cells from their specification to their colonization of the genital ridges. We show that at around E8.0, germ cells concomitantly and significantly reduce H3-K9 dimethylation and DNA methylation, two major repressive modifications for gene expression. These events are preceded by the transient loss of all the DNA methyltransferases from their nuclei. By contrast, germ cells substantially increase the levels of H3-K27 trimethylation, another repressive modification with more plasticity, at E8.5-9.0 and maintain this state until at least E12.5. H3-K4 methylation and H3-K9 acetylation, modifications associated with transcriptionally permissive/active chromatin, are similar in germ and surrounding somatic cells but germ cells transiently increase these marks sharply upon their entry into the genital ridge. H3-K9 trimethylation, a hallmark of centromeric heterochromatin, is kept relatively constant during the periods examined. We suggest that this orderly and extensive epigenetic reprogramming in premigratory and migratory germ cells might be necessary for their reacquisition of underlying totipotency, for subsequent specific epigenetic remodeling, including the resetting of parental imprints, and for the production of gametes with an appropriate epigenotype for supporting normal development. (C) 2004 Elsevier Inc. All rights reserved.