Histone methyltransferases MES-4 and MET-1 promote meiotic checkpoint activation in Caenorhabditis elegans.
Histone methyltransferases MES-4 and MET-1 promote meiotic checkpoint activation in Caenorhabditis elegans.
复制标题
组蛋白甲基转移酶MES-4和MET-1促进秀丽隐杆线虫中的减数分裂检查点。
DOI：
10.1371/journal.pgen.1003089
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Bhalla N
中科院分区：
文献类型：
--
作者：
Lamelza P;Bhalla N
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. Sexual reproduction relies on meiosis. This specialized cell division generates gametes, such as sperm and eggs, with a single copy of the genome so that fertilization restores diploidy. During meiosis, homologous chromosomes undergo synapsis, in which they assemble a proteinaceous structure called the synaptonemal complex to promote proper chromosome segregation. In C. elegans, a checkpoint monitors synapsis and removes nuclei that have unsynapsed chromosomes by activating programmed cell death or apoptosis. Activation of this checkpoint coincides with, but is not dependent on, the assembly of heterochromatin on unsynapsed chromosomes. The acquisition of heterochromatic marks is a conserved response to asynapsis. A specific portion of each chromosome, called a Pairing Center (PC), is required for this checkpoint; but how PCs send a signal when chromosomes are unsynapsed is unknown. We present evidence that suggests that unsynapsed PCs need to maintain a transcriptionally open chromatin environment, even as the rest of the chromosome undergoes heterochromatin assembly, to activate the checkpoint. Furthermore, 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.
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