Trans-generational epigenetic regulation of C. elegans primordial germ cells.
Trans-generational epigenetic regulation of C. elegans primordial germ cells.
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DOI：
10.1186/1756-8935-3-15
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发表时间：
2010-08-12
影响因子：
3.9
通讯作者：
Kelly WG
中科院分区：
文献类型：
--
作者：
Furuhashi H;Takasaki T;Rechtsteiner A;Li T;Kimura H;Checchi PM;Strome S;Kelly WG
生殖系在几代人之间保持连续性的过程一直是生物学研究的重点。最近的研究表明，种系连续性可能涉及表观遗传调控，包括组蛋白修饰的调控。然而，目前尚不清楚在一代中产生的组蛋白修饰如何影响转录程序和下一代生殖细胞的发育。我们发现组蛋白H3 K36甲基转移酶母体效应不育（MES）-4是一种表观遗传修饰剂，可防止秀丽隐杆线虫原始生殖细胞（PGCs）的异常转录活性。在mes-4突变型PGCs中，RNA Pol II激活受到异常调节，PGCs退化。MES-4介导的H3 K36甲基化的遗传和全基因组分析表明，MES-4活性可以独立于正在进行的转录而运作，并且可能主要负责维持生殖系表达基因座中H3 K36的甲基化。我们的数据表明，MES-4有助于维持前几代生殖细胞中发生的转录的“表观遗传记忆”，并且MES-4及其表观遗传产物对正常生殖细胞发育至关重要。
The processes through which the germline maintains its continuity across generations has long been the focus of biological research. Recent studies have suggested that germline continuity can involve epigenetic regulation, including regulation of histone modifications. However, it is not clear how histone modifications generated in one generation can influence the transcription program and development of germ cells of the next. We show that the histone H3K36 methyltransferase maternal effect sterile (MES)-4 is an epigenetic modifier that prevents aberrant transcription activity in Caenorhabditis elegans primordial germ cells (PGCs). In mes-4 mutant PGCs, RNA Pol II activation is abnormally regulated and the PGCs degenerate. Genetic and genomewide analyses of MES-4-mediated H3K36 methylation suggest that MES-4 activity can operate independently of ongoing transcription, and may be predominantly responsible for maintenance methylation of H3K36 in germline-expressed loci. Our data suggest a model in which MES-4 helps to maintain an 'epigenetic memory' of transcription that occurred in germ cells of previous generations, and that MES-4 and its epigenetic product are essential for normal germ cell development.
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