Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes.
Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes.
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DOI：
10.1007/s00412-013-0438-5
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发表时间：
2014-03
期刊：
影响因子：
1.6
通讯作者：
San-Segundo PA
中科院分区：
文献类型：
--
作者：
Ontoso D;Kauppi L;Keeney S;San-Segundo PA
在减数分裂前期I，母本和父本染色体之间的相互作用，在检查点监视下，建立同源物之间的连接，促进其准确分布到减数分裂后代。在人类中，错误的减数分裂会导致非整倍体，从而导致流产和遗传疾病。减数分裂过程发生在染色质的背景下，因此组蛋白翻译后修饰预计将发挥重要作用。在这里，我们报告的细胞学分布的进化保守的DOT 1 L甲基转移酶和不同的H3 K79甲基化状态导致其活动（单，双和三甲基化; H3 K79 me 1，me 2和me 3，分别）在小鼠精母细胞减数分裂前期I。在野生型，而低量的H3 K79 me 1是相当均匀地存在于整个前期I，DOT 1 L，H3 K79 me 2和H3 K79 me 3的水平表现出显着的增加，从粗线向前，但与差异亚核分布模式。异染色质的着丝粒区域和性体富集H3 K79 me 3。相反，H3 K79 me 2存在于整个染色质中，但尽管DOT 1 L积累，但在很大程度上被排除在性体之外。在减数分裂缺陷的小鼠突变体中，DOT 1 L和H3 K79 me的增加在减数分裂停滞的同一阶段被阻断。H3 K79 me模式结合H3.3、γ H2 AX、macroH 2A和H2A.Z组蛋白变体的细胞学分析，与这些表观遗传标记在雄性小鼠减数分裂前期I中的差异作用一致。我们认为H3 K79 me 2与粗线期常染色体上的转录再激活有关，而H3 K79 me 3可能有助于维持着丝粒区域和性体的抑制性染色质。
During meiotic prophase I, interactions between maternal and paternal chromosomes, under checkpoint surveillance, establish connections between homologs that promote their accurate distribution to meiotic progeny. In human, faulty meiosis causes aneuploidy resulting in miscarriages and genetic diseases. Meiotic processes occur in the context of chromatin, therefore histone post-translational modifications are expected to play important roles. Here, we report the cytological distribution of the evolutionarily conserved DOT1L methyltransferase and the different H3K79 methylation states resulting from its activity (mono-, di- and tri-methylation; H3K79me1, me2 and me3, respectively) during meiotic prophase I in mouse spermatocytes. In the wild type, whereas low amounts of H3K79me1 are rather uniformly present throughout prophase I, levels of DOT1L, H3K79me2 and H3K79me3 exhibit a notable increase from pachynema onwards, but with differential subnuclear distribution patterns. The heterochromatic centromeric regions and the sex body are enriched for H3K79me3. In contrast, H3K79me2 is present all over the chromatin, but is largely excluded from the sex body despite the accumulation of DOT1L. In meiosis-defective mouse mutants, the increase of DOT1L and H3K79me is blocked at the same stage where meiosis is arrested. H3K79me patterns, combined with the cytological analysis of the H3.3, γH2AX, macroH2A and H2A.Z histone variants, are consistent with a differential role for these epigenetic marks in male mouse meiotic prophase I. We propose that H3K79me2 is related to transcriptional reactivation on autosomes during pachynema, whereas H3K79me3 may contribute to the maintenance of repressive chromatin at centromeric regions and the sex body.
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