title: Histone methyltransferases MES-4 and MET-1 promote meiotic checkpoint activation in Caenorhabditis elegans.
abstract: Chromosomes that fail to synapse during meiosis become enriched for chromatin marks associated with heterochromatin assembly. This response, called meiotic silencing of unsynapsed or unpaired chromatin (MSUC), is conserved from fungi to mammals. In Caenorhabditis elegans, unsynapsed chromosomes also activate a meiotic checkpoint that monitors synapsis. The synapsis checkpoint signal is dependent on cis-acting loci called Pairing Centers (PCs). How PCs signal to activate the synapsis checkpoint is currently unknown. We show that a chromosomal duplication with PC activity is sufficient to activate the synapsis checkpoint and that it undergoes heterochromatin assembly less readily than a duplication of a non-PC region, suggesting that the chromatin state of these loci is important for checkpoint function. Consistent with this hypothesis, MES-4 and MET-1, chromatin-modifying enzymes associated with transcriptional activity, are required for the synapsis checkpoint. In addition, a duplication with PC activity undergoes heterochromatin assembly when mes-4 activity is reduced. MES-4 function is required specifically for the X chromosome, while MES-4 and MET-1 act redundantly to monitor autosomal synapsis. We propose that MES-4 and MET-1 antagonize heterochromatin assembly at PCs of unsynapsed chromosomes by promoting a transcriptionally permissive chromatin environment that is required for meiotic checkpoint function. Moreover, we suggest that different genetic requirements to monitor the behavior of sex chromosomes and autosomes allow for the lone unsynapsed X present in male germlines to be shielded from inappropriate checkpoint activation.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
authors.forename: Piero
authors.initials: P
authors.lastname: Lamelza
authors.forename: Needhi
authors.initials: N
authors.lastname: Bhalla
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D023902:Chromosome Pairing / Q000235:genetics*; D020868:Gene Silencing; D018816:Genes, cdc / Q000235:genetics; D005854:Germ Cells; D006570:Heterochromatin / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D012730:Sex Chromosomes
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; C449639:Mes-4 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; C523530:Met-1 protein, C elegans