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.
Highlights
Meiosis is the specialized cell division in which a diploid cell gives rise to haploid gametes, such as eggs and sperm
We present evidence that suggests that unsynapsed Pairing Centers (PCs) need to maintain a transcriptionally open chromatin environment, even as the rest of the chromosome undergoes heterochromatin assembly, to activate the checkpoint
We demonstrate that sex chromosomes have different genetic requirements than autosomes to monitor synapsis, providing a potential explanation for observed sexual dimorphism in synapsis checkpoint activation
Summary
Meiosis is the specialized cell division in which a diploid cell gives rise to haploid gametes, such as eggs and sperm. To ensure that chromosomes segregate properly in meiosis and produce gametes with the correct number of chromosomes, homologous chromosomes undergo meiosisspecific events to generate a linkage, or chiasma, that enables proper biorientation on the meiotic spindle. Homologous chromosomes identify their unique partner to pair, stabilize this pairing by assembling a proteinaceous structure called the synaptonemal complex (SC) between homologs and undergo homologous recombination in the context of the SC. Defects in SC formation prevent or severely reduce homologous recombination [1] and can produce gametes with an incorrect chromosome complement. It is estimated that 30% of miscarriages are the product of meiotic chromosome missegregation [2]
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