Epigenetic control of ovarian function: The emerging role of histone modifications
Epigenetic control of ovarian function: The emerging role of histone modifications
复制标题
DOI：
10.1016/j.mce.2005.09.005
复制
发表时间：
2005-11-24
影响因子：
4.1
通讯作者：
LaVoie, HA
中科院分区：
文献类型：
--
作者：
LaVoie, HA
卵巢滤泡的动态性质使其成为研究与细胞生长和分化相关的基因协调激活和失活的理想模型。在鉴定促进卵巢基因转录的转录因子方面已经取得了很大进展，这些基因介导促性腺激素作用和类固醇生成，但这些因子如何在染色质中促进转录还不清楚。在过去的5年中，通过组蛋白修饰对卵巢基因的表观遗传调控已成为越来越多的研究的焦点。事实上，与转录因子相关的几种辅激活子和辅抑制子分别是组蛋白乙酰转移酶和组蛋白脱乙酰酶，它们分别介导组蛋白的超乙酰化和低乙酰化。核心组蛋白尾部赖氨酸残基的超乙酰化促进有利于转录的染色质改变，而组蛋白的低乙酰化促进基因沉默或抑制。不仅核心组蛋白的乙酰化状态决定了染色质重塑是否发生，而且组蛋白磷酸化和甲基化可能起同样重要的作用。例如，组蛋白H3磷酸化和乙酰化的组合一致地有利于转录。此外，特异性赖氨酸甲基化（例如，组蛋白H3的K9）抑制基因表达，而其他甲基化促进基因表达。最有可能的是组蛋白修饰事件的组合调节转录的起始。了解卵巢激素如何控制特定的组蛋白修饰将有助于我们了解卵泡细胞如何从控制细胞增殖的活跃基因库转换为控制终末分化的基因组。在阐明组蛋白修饰酶的卵巢特异性调节以及在卵泡周期的不同阶段确定其靶基因库的进展，预计在未来几年。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The dynamic nature of the ovarian follicle makes it an ideal model to study the coordinated activation and inactivation of genes related to cell growth and differentiation. Much progress has been made in identifying transcription factors that promote the transcription of ovarian genes mediating gonadotropin action and steroidogenesis, but how these factors promote transcription in the context of chromatin is not well understood. Over the past 5 years, epigenetic regulation of ovarian genes through histone modifications has been the focus of an increasing number of studies. Several coactivators and corepressors associated with transcription factors are in fact histone acetyltransferases and histone deacetylases mediating the hyperacetylation and hypoacetylation of histones, respectively. Hyperacetylation of lysine residues in the core histone tails promotes chromatin alterations that favor transcription, whereas hypoacetylation of histones promotes gene silencing or repression. Not only does the acetylation status of the core histones determine whether chromatin remodeling occurs, but histone phosphorylation and methylation may serve equally important roles. For example, the combination of histone H3 phosphorylation and acetylation concertedly favors transcription. In addition, specific lysine methylations (e.g., K9 of histone H3) repress gene expression whereas other methylations promote gene expression. It is most likely the combination of histone modification events that regulate the initiation of transcription. Understanding how ovarian hormones control specific histone modifications will help us understand how follicular cells can switch from active gene pools governing cell proliferation to those gene groups controlling terminal differentiation. Progress in elucidating the ovarian specific regulation of histone modifying enzymes as well as identification of their target gene pools at different stages of the follicular cycle is expected in the next few years. (c) 2005 Elsevier Ireland Ltd. All rights reserved.