RIKEN Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Development. 2011 Oct;138(19):4207-17. doi: 10.1242/dev.064444.
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 HP1γ. We further found that centromere clustering and synapsis were commonly affected in G9a- and Cbx3-deficient spermatocytes. These genetic observations suggest that HP1γ/G9a-dependent PCH-mediated centromere clustering is an axis for proper chromosome interactions during meiotic prophase. We propose that the role of the HP1γ/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.
在减数分裂过程中，着丝粒周围异染色质（PCH）的特定组蛋白修饰，特别是组蛋白 H3 赖氨酸 9 的三甲基化和二甲基化（分别为 H3K9me3 和 H3K9me2），对于正确的染色体相互作用是必需的。然而，H3K9 甲基化介导联会的分子机制尚不清楚。我们已经生成了 Cbx3 缺陷型小鼠品系，并对 Suv39h1/h2、G9a 和 Cbx3 缺陷型精母细胞进行了比较分析。这项研究揭示了 PCH 处的 H3K9me2 依赖于 Suv39h1/h2 介导的 H3K9me3 及其被 Cbx3 基因产物 HP1γ 的识别。我们进一步发现 G9a 和 Cbx3 缺陷型精母细胞中着丝粒簇集和联会均受到共同影响。这些遗传观察表明，HP1γ/G9a 依赖的 PCH 介导的着丝粒簇集是减数分裂前期正确染色体相互作用的一个轴。我们提出，HP1γ/G9a 轴的作用是将未配对同源染色体的着丝粒区域保持在紧密排列，并促进其在减数分裂早期的配对进展。这项研究还揭示了不同组蛋白修饰之间相互作用的相当大的灵活性，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。
