A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line.
A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line.
复制标题
DOI：
10.1371/journal.pgen.1001349
复制
发表时间：
2011-03
期刊：
影响因子：
4.5
通讯作者：
Kelly WG
中科院分区：
文献类型：
--
作者：
Li T;Kelly WG
组蛋白H3赖氨酸4甲基化（H3 K4 me）是表观遗传调控的重要组成部分。H3 K4甲基化是转录活性的结果，但也已显示有助于“表观遗传记忆”;即，它可以提供先前转录活性的可遗传标志，其可以帮助在随后的细胞后代或谱系中促进或维持这种活性。在几种生物体中已经描述了许多控制H3 K4 me添加的多蛋白质复合物。这些Set 1/MLL或COMPASS复合物通常共享保守蛋白的共同子集，其他组分可能有助于甲基转移酶活性的组织特异性或发育调节。在这里，我们表明，H3 K4的二甲基化和三甲基化在秀丽隐杆线虫的生殖系的正常维护是依赖于同源的Set 1/MLL复合物组件WDR-5.1和RBBP-5。依赖于wdr-5.1和rbbp-5的不同甲基化状态需要不同的甲基转移酶。此外，不同子集的保守Set 1/MLL样复合物组件似乎需要在不同发育阶段的生殖细胞和体细胞谱系中的H3 K4甲基化。在成体生殖细胞中，wdr-5.1或rbbp-5的突变显著影响生殖系干细胞（GSC）群体大小和适当的生殖细胞发育。RNA聚合酶II的RNAi敲低并不显著影响早期胚胎或成年GSC中H3 K4甲基化的wdr-5.1依赖性维持，表明该机制并不与这些细胞中的转录特异性偶联。一个单独的，wdr-5.1独立的H3 K4甲基化模式更直接地与成年生殖系和胚胎中的转录相关。我们的研究结果表明，H3 K4甲基化在生殖细胞的调节组合Set 1/MLL组件依赖和独立的模式表观遗传的建立和维护。生殖系在两代人之间传递遗传和表观遗传信息。种系独特地保留了发育全能性，生殖细胞的这种特性可能嵌入在整个种系周期、每一代内和每一代之间保留的表观遗传信息中。组蛋白H3在赖氨酸4上的甲基化（H3 K4 me）已被鉴定为活跃转录的标志和“表观遗传记忆”的潜在组分。我们证明了C.保守的H3 K4甲基转移酶复合物Set 1/MLL复合物的组分的elegans同源物对于C.线虫生殖细胞和早期胚胎。有趣的是，Set 1/MLL组分依赖性H3 K4甲基化可以独立于早期胚胎生殖系和体细胞卵裂球中的转录而发生，并且也可以在成体生殖系干细胞中发生。一个单独的H3 K4甲基化机制，独立于Set 1/MLL组件活动似乎更依赖于正在进行的转录。我们假设H3 K4甲基化通过交替的转录依赖性和非依赖性机制在整个生殖细胞周期中维持，该机制维持生殖系表观基因组的这一组分。
The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute to “epigenetic memory”; i.e., it can provide a heritable landmark of previous transcriptional activity that may help promote or maintain such activity in subsequent cell descendants or lineages. A number of multi-protein complexes that control the addition of H3K4me have been described in several organisms. These Set1/MLL or COMPASS complexes often share a common subset of conserved proteins, with other components potentially contributing to tissue-specific or developmental regulation of the methyltransferase activity. Here we show that the normal maintenance of H3K4 di- and tri-methylation in the germ line of Caenorhabditis elegans is dependent on homologs of the Set1/MLL complex components WDR-5.1 and RBBP-5. Different methylation states that are each dependent on wdr-5.1 and rbbp-5 require different methyltransferases. In addition, different subsets of conserved Set1/MLL-like complex components appear to be required for H3K4 methylation in germ cells and somatic lineages at different developmental stages. In adult germ cells, mutations in wdr-5.1 or rbbp-5 dramatically affect both germ line stem cell (GSC) population size and proper germ cell development. RNAi knockdown of RNA Polymerase II does not significantly affect the wdr-5.1–dependent maintenance of H3K4 methylation in either early embryos or adult GSCs, suggesting that the mechanism is not obligately coupled to transcription in these cells. A separate, wdr-5.1–independent mode of H3K4 methylation correlates more directly with transcription in the adult germ line and in embryos. Our results indicate that H3K4 methylation in the germline is regulated by a combination of Set1/MLL component-dependent and -independent modes of epigenetic establishment and maintenance. The germ line transmits both genetic and epigenetic information between and across generations. The germ line uniquely retains developmental totipotency, and this property of germ cells is likely embedded in epigenetic information that is retained throughout the germ line cycle, within and across each generation. The methylation of Histone H3 on Lysine 4 (H3K4me) has been identified as both a mark of active transcription and a potential component of “epigenetic memory.” We show that C. elegans homologs of components of a conserved H3K4 methyltransferase complex, the Set1/MLL complex, are important for normal H3K4 methylation in C. elegans germ cells and early embryos. Interestingly, Set1/MLL component dependent H3K4 methylation can occur independently of transcription in early embryonic germline and somatic blastomeres, and also in adult germline stem cells. A separate H3K4 methylation mechanism that operates independently of Set1/MLL component activities appears more dependent on ongoing transcription. We hypothesize that H3K4 methylation is maintained throughout the germ cell cycle by alternating transcription-dependent and -independent mechanisms that maintain this component of the germline epigenome.
登录
查看更多内容
影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1111/j.1742-4658.2010.07609.x
发表时间：
2010-04
期刊：
The FEBS journal
影响因子：
--
作者：
Cosgrove MS;Patel A
通讯作者：
Patel A
影响因子：
16.8
作者：
Brykczynska, Urszula;Hisano, Mizue;Peters, Antoine H. F. M.
通讯作者：
Peters, Antoine H. F. M.
影响因子：
4.6
作者：
Glaser, S;Schaft, J;Stewart, AF
通讯作者：
Stewart, AF