caenorhabditis elegans histone methyltransferase met-2 shields the male x chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation秀丽隐杆线虫组蛋白甲基转移酶met-2盾牌男性从检查站机械和x染色体介导减数分裂性染色体失活.pdfVIP

Caenorhabditis elegans Histone Methyltransferase MET- 2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation Paula M. Checchi, JoAnne Engebrecht* Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America Abstract Meiosis is a specialized form of cellular division that results in the precise halving of the genome to produce gametes for sexual reproduction. Checkpoints function during meiosis to detect errors and subsequently to activate a signaling cascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpoint response that can in turn trigger germline apoptosis. In a heterogametic germ line, however, sex chromosomes proceed through meiosis with unsynapsed regions and are not recognized by checkpoint machinery. We conducted a directed RNAi screen in Caenorhabditis elegans to identify regulatory factors that prevent recognition of heteromorphic sex chromosomes as unpaired and uncovered a role for the SET domain histone H3 lysine 9 histone methyltransferase (HMTase) MET-2 and two additional HMTases in shielding the male X from checkpoint machinery. We found that MET-2 also mediates the transcriptional silencing program of meiotic sex chromosome inactivation (MSCI) but not meiotic silencing of unsynapsed chromatin (MSUC), suggesting that these processes are distinct. Further, MSCI and checkpoint shielding can be uncoupled, as double-strand breaks targeted to an unpaired, transcriptionally silenced extra-chromosomal array induce checkpoint activation in germ lines depleted for met-2. In summary, our data uncover a mechanism by which repressive chromatin architecture enables checkpoint proteins to d