HP1γ links histone methylation marks to meiotic synapsis in mice
HP1γ links histone methylation marks to meiotic synapsis in mice
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DOI：
10.1242/dev.064444
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发表时间：
2011-10-01
期刊：
影响因子：
4.6
通讯作者：
Koseki, Haruhiko
中科院分区：
文献类型：
--
作者：
Takada, Yuki;Naruse, Chie;Koseki, Haruhiko
在减数分裂期间，在臂间异染色质（PCH）处的特定组蛋白修饰，特别是组蛋白H3在赖氨酸9处的三甲基化和二甲基化（分别为H3 K9 me 3和H3 K9 me 2），是正确的染色体相互作用所必需的。然而，H3 K9甲基化介导突触的分子机制尚不清楚。我们已经产生了一个Cbx 3-缺陷的小鼠系，并进行了比较分析Suv 39 h1/h2-，G9 a-和Cbx 3-缺陷的精母细胞。这项研究表明，PCH上的H3 K9 me 2依赖于Suv 39 h1/h2介导的H3 K9 me 3及其被Cbx 3基因产物HP 1 γ识别。我们进一步发现，着丝粒聚集和突触在G9 a和Cbx 3缺陷的精母细胞中普遍受到影响。这些遗传观察表明，HP 1 γ/G9 a依赖的PCH介导的着丝粒聚类是一个轴，在减数分裂前期适当的染色体相互作用。我们建议，HP 1 γ/G9 a轴的作用是保留着丝粒区的未配对的同源染色体紧密对齐，并促进其配对的进展，在早期减数分裂前期。这项研究还揭示了相当大的可塑性，在不同的组蛋白修饰之间的相互作用，并表明，这种逐步和动态的表观遗传修饰可能在减数分裂中发挥关键作用。
During meiosis, specific histone modifications at pericentric heterochromatin (PCH), especially histone H3 tri- and dimethylation at lysine 9 (H3K9me3 and H3K9me2, respectively), are required for proper chromosome interactions. However, the molecular mechanism by which H3K9 methylation mediates the synapsis is not yet understood. We have generated a Cbx3-deficient mouse line and performed comparative analysis on Suv39h1/h2-, G9a- and Cbx3-deficient spermatocytes. This study revealed that H3K9me2 at PCH depended on Suv39h1/h2- mediated H3K9me3 and its recognition by the Cbx3 gene product HP1 gamma. We further found that centromere clustering and synapsis were commonly affected in G9a- and Cbx3-deficient spermatocytes. These genetic observations suggest that HP1 gamma/G9a-dependent PCH-mediated centromere clustering is an axis for proper chromosome interactions during meiotic prophase. We propose that the role of the HP1 gamma/G9a axis is to retain centromeric regions of unpaired homologous chromosomes in close alignment and facilitate progression of their pairing in early meiotic prophase. This study also reveals considerable plasticity in the interplay between different histone modifications and suggests that such stepwise and dynamic epigenetic modifications may play a pivotal role in meiosis.