A histone H3 methyltransferase controls epigenetic events required for meiotic prophase
A histone H3 methyltransferase controls epigenetic events required for meiotic prophase
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DOI：
10.1038/nature04112
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发表时间：
2005-11-17
期刊：
影响因子：
64.8
通讯作者：
Matsui, Y
中科院分区：
文献类型：
--
作者：
Hayashi, K;Yoshida, K;Matsui, Y
组蛋白的表观遗传修饰调节基因表达和染色质结构（1，2）。在这里，我们表明，Meisetz（减数分裂诱导因子含有PR/SET结构域和锌指基序）是一个组蛋白甲基转移酶，是重要的早期减数分裂前期的进展。Meisetz转录本仅在女性胎儿性腺和出生后睾丸中进入减数分裂前期的生殖细胞中检测到。值得注意的是，Meisetz对组蛋白H3的赖氨酸4的三甲基化具有催化活性，但不具有单甲基化或二甲基化，并且具有依赖于其甲基化活性的反式激活活性。Meisetz基因被破坏的小鼠由于双链断裂修复途径严重受损、同源染色体配对缺陷和性小体形成受损而在两种性别中显示不育。在Meisetz缺陷的睾丸中，组蛋白H3的赖氨酸4的三甲基化被减弱，并且减数分裂基因转录被改变。这些发现表明，哺乳动物减数分裂特异性表观遗传事件对减数分裂的正常进行至关重要。
Epigenetic modifications of histones regulate gene expression and chromatin structure(1,2). Here we show that Meisetz (meiosis-induced factor containing a PR/SET domain and zinc-finger motif) is a histone methyltransferase that is important for the progression of early meiotic prophase. Meisetz transcripts are detected only in germ cells entering meiotic prophase in female fetal gonads and in postnatal testis. Notably, Meisetz has catalytic activity for trimethylation, but not mono- or dimethylation, of lysine 4 of histone H3, and a transactivation activity that depends on its methylation activity. Mice in which the Meisetz gene is disrupted show sterility in both sexes due to severe impairment of the double-stranded break repair pathway, deficient pairing of homologous chromosomes and impaired sex body formation. In Meisetz-deficient testis, trimethylation of lysine 4 of histone H3 is attenuated and meiotic gene transcription is altered. These findings indicate that meiosis-specific epigenetic events in mammals are crucial for proper meiotic progression.