Caenorhabditis elegans Histone Methyltransferase MET-2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation
Caenorhabditis elegans Histone Methyltransferase MET-2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation
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 distinguish between the partnerless male X chromosome and asynapsed chromosomes thereby shielding the lone X from inappropriate activation of an apoptotic program.
- University of California, San Francisco United States
- University of California, Davis United States
Male, 570, X Chromosome, Transcription, Genetic, 1.1 Normal biological development and functioning, 610, Apoptosis, QH426-470, Histones, Genetic, X Chromosome Inactivation, Genetics, Animals, Gene Silencing, cdc, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Contraception/Reproduction, Prevention, Lysine, Human Genome, Histone-Lysine N-Methyltransferase, Biological Sciences, Chromatin, Genes, cdc, Meiosis, Germ Cells, Genes, Biochemistry and Cell Biology, Generic health relevance, Transcription, Developmental Biology, Research Article
Male, 570, X Chromosome, Transcription, Genetic, 1.1 Normal biological development and functioning, 610, Apoptosis, QH426-470, Histones, Genetic, X Chromosome Inactivation, Genetics, Animals, Gene Silencing, cdc, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Contraception/Reproduction, Prevention, Lysine, Human Genome, Histone-Lysine N-Methyltransferase, Biological Sciences, Chromatin, Genes, cdc, Meiosis, Germ Cells, Genes, Biochemistry and Cell Biology, Generic health relevance, Transcription, Developmental Biology, Research Article
48 Research products, page 1 of 5
- 2017IsRelatedTo
- 2019IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2018IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).35 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
