Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis.
Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis.
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Polycomb蛋白SCML2与USP7相关，并在雄性减数分裂过程中抵消XY染色质的组蛋白H2A泛素化。
DOI：
10.1371/journal.pgen.1004954
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发表时间：
2015-01
期刊：
影响因子：
4.5
通讯作者：
Wang PJ
中科院分区：
文献类型：
--
作者：
Luo M;Zhou J;Leu NA;Abreu CM;Wang J;Anguera MC;de Rooij DG;Jasin M;Wang PJ
多梳蛋白在不同发育过程中介导转录沉默。性染色体在雄性减数分裂过程中经历染色体范围的转录沉默。在这里，我们报道了小鼠SCML2(Sex Comb on MidLeg-like 2)，一种X染色体编码的多梳蛋白，在包括精原细胞、精母细胞和圆形精子细胞在内的生殖细胞中特异表达。SCML2与磷酸化的H2AX结合，定位于精母细胞中的XY小体。在小鼠中，SCML2的缺失会导致精子发生缺陷，导致精子产量急剧下降。在精母细胞中，SCML2与脱泛素酶USP7相互作用，并将其招募到XY小体。在没有SCML2的情况下，USP7不能在XY体内积聚，而H2A的单泛素化在XY染色质中显著增加。我们的结果表明，SCML2/USP7复合体是调控雄性减数分裂中性染色体表观遗传状态的一条新的分子途径。染色质修饰酶在发育和疾病过程中调节染色质状态。多梳蛋白通过催化染色质的组蛋白核心蛋白成分的翻译后修饰来控制发育模式中同源异型基因的表达。大多数研究都集中在广泛表达的多梳蛋白上。然而，人们对多梳蛋白在组织中的特定作用知之甚少。在这里，我们报道了一种睾丸特异的多梳蛋白-SCML2的功能研究。Scml2基因定位于X染色体。有趣的是，在雄性减数分裂过程中，SCML2蛋白特异性地定位于生殖细胞中的XY染色质，这经历了染色体范围的转录沉默。Scml2基因的破坏会导致小鼠精子发生的缺陷。SCML2与磷酸化的H_2AX和脱泛素酶USP7结合。虽然磷酸化的H2AX对XY染色质的定位不依赖于SCML2，但USP7以SCML2依赖的方式定位于XY染色质。SCML2的缺失导致精母细胞的XY染色质中H_2A单泛素化的积累。这些对SCML2的功能研究揭示了在雄性减数分裂过程中调节性染色体上的H_2A泛素化的新的分子途径。
Polycomb group proteins mediate transcriptional silencing in diverse developmental processes. Sex chromosomes undergo chromosome-wide transcription silencing during male meiosis. Here we report that mouse SCML2 (Sex comb on midleg-like 2), an X chromosome-encoded polycomb protein, is specifically expressed in germ cells, including spermatogonia, spermatocytes, and round spermatids. SCML2 associates with phosphorylated H2AX and localizes to the XY body in spermatocytes. Loss of SCML2 in mice causes defective spermatogenesis, resulting in sharply reduced sperm production. SCML2 interacts with and recruits a deubiquitinase, USP7, to the XY body in spermatocytes. In the absence of SCML2, USP7 fails to accumulate on the XY body, whereas H2A monoubiquitination is dramatically augmented in the XY chromatin. Our results demonstrate that the SCML2/USP7 complex constitutes a novel molecular pathway in modulating the epigenetic state of sex chromosomes during male meiosis. Chromatin-modifying enzymes regulate the chromatin state during development and disease. Polycomb group proteins control the expression of homeotic genes in developmental patterning by catalyzing post-translational modifications of histones—core protein components of the chromatin. Most studies have focused on widely expressed polycomb proteins. However, the tissue-specific roles of polycomb proteins are poorly understood. Here we report functional studies of a testis-specific polycomb protein—SCML2. The Scml2 gene maps to the X chromosome. Intriguingly, the SCML2 protein localizes specifically to the XY chromatin in germ cells during male meiosis, which undergoes chromosome-wide transcriptional silencing. Disruption of Scml2 causes defects in spermatogenesis in mice. SCML2 associates with phosphorylated H2AX and a deubiquitinase, USP7. While localization of phosphorylated H2AX to the XY chromatin is SCML2-independent, USP7 localizes to the XY chromatin in an SCML2-dependent manner. Loss of SCML2 results in accumulation of H2A monoubiquitination in the XY chromatin in spermatocytes. These functional studies of SCML2 uncover a new molecular pathway that regulates H2A ubiquitination on the sex chromosomes during male meiosis.
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影响因子：
11.8
作者：
Lu, Lin-Yu;Wu, Jiaxue;Ye, Lin;Gavrilina, Galina B.;Saunders, Thomas L.;Yu, Xiaochun
通讯作者：
Yu, Xiaochun
影响因子：
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DOI：
10.1016/j.bbrc.2010.08.082
发表时间：
2010-09-24
影响因子：
3.1
作者：
de Bie, Prim;Zaaroor-Regev, Daphna;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
9.8
作者：
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通讯作者：
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