Role of polycomb group protein cbx2/m33 in meiosis onset and maintenance of chromosome stability in the Mammalian germline.
Role of polycomb group protein cbx2/m33 in meiosis onset and maintenance of chromosome stability in the Mammalian germline.
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DOI：
10.3390/genes2010059
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发表时间：
2011
期刊：
影响因子：
3.5
通讯作者：
De La Fuente R
中科院分区：
文献类型：
--
作者：
Baumann C;De La Fuente R
多梳族蛋白 (PcG) 是主要的表观遗传调节因子，对于建立发育控制基因的可遗传表达模式至关重要。小鼠 PcG 家族成员 M33/Cbx2（Chromobox 同源蛋白 2）是 Polycomb 抑制复合物 1 (PRC1) 的组成部分。小鼠中 Cbx2/M33 的靶向缺失会导致中轴骨骼的同源异型转变、生长迟缓和雄性到雌性的性别逆转。在这项研究中，我们测试了 Cbx2 是否参与减数分裂过程中染色质重塑过程的控制。我们的分析显示，28.6% 的 XY−/− 胚胎出现性逆转，其中观察到发育不良的睾丸和靠近肾脏的对侧卵巢，而其余的男性突变胎儿则表现出双侧睾丸发育不全。值得注意的是，在胎儿发育第 18.5 天从 Cbx2(XY−/−) 睾丸中回收的生殖细胞表现出减数分裂过早开始，并形成联会复合体，表明 Cbx2 在控制雄性生殖细胞减数分裂进入中发挥作用。突变雌性在粗线期表现出小卵巢，具有显着的生殖细胞损失和高比例的卵母细胞具有异常突触和非同源相互作用，以及在双线期形成单价体。这些缺陷与未能解决粗线期晚期以持续性 γH2AX 和 Rad51 病灶为标志的 DNA 双链断裂有关。重要的是，减数分裂沉默非突触染色质所需的两个因素，泛素化组蛋白 H2A (ubH2A) 和染色质重塑蛋白 BRCA1，与大多数 Cbx2(−/−) 卵母细胞中完全突触的染色体轴共定位。这些结果提供了新的证据，表明 Cbx2 在哺乳动物种系的生殖细胞活力、减数分裂开始和同源染色体突触中发挥着关键的、以前未被认识到的作用。
Polycomb group proteins (PcG) are major epigenetic regulators, essential for establishing heritable expression patterns of developmental control genes. The mouse PcG family member M33/Cbx2 (Chromobox homolog protein 2) is a component of the Polycomb-Repressive Complex 1 (PRC1). Targeted deletion of Cbx2/M33 in mice results in homeotic transformations of the axial skeleton, growth retardation and male-to-female sex reversal. In this study, we tested whether Cbx2 is involved in the control of chromatin remodeling processes during meiosis. Our analysis revealed sex reversal in 28.6% of XY−/− embryos, in which a hypoplastic testis and a contralateral ovary were observed in close proximity to the kidney, while the remaining male mutant fetuses exhibited bilateral testicular hypoplasia. Notably, germ cells recovered from Cbx2(XY−/−) testes on day 18.5 of fetal development exhibited premature meiosis onset with synaptonemal complex formation suggesting a role for Cbx2 in the control of meiotic entry in male germ cells. Mutant females exhibited small ovaries with significant germ cell loss and a high proportion of oocytes with abnormal synapsis and non-homologous interactions at the pachytene stage as well as formation of univalents at diplotene. These defects were associated with failure to resolve DNA double strand breaks marked by persistent γH2AX and Rad51 foci at the late pachytene stage. Importantly, two factors required for meiotic silencing of asynapsed chromatin, ubiquitinated histone H2A (ubH2A) and the chromatin remodeling protein BRCA1, co-localized with fully synapsed chromosome axes in the majority of Cbx2(−/−) oocytes. These results provide novel evidence that Cbx2 plays a critical and previously unrecognized role in germ cell viability, meiosis onset and homologous chromosome synapsis in the mammalian germline.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
DOI：
10.1073/pnas.0801521105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Colas, Isabelle;Shaw, Peter;Moore, Graham
通讯作者：
Moore, Graham
影响因子：
56.9
作者：
Bowles, J;Knight, D;Koopman, P
通讯作者：
Koopman, P
影响因子：
2.7
作者：
De La Fuente, R;Viveiros, MM;Eppig, JJ
通讯作者：
Eppig, JJ
影响因子：
21.3
作者：
Ancelin, Katia;Lange, Ulrike C.;Surani, M. Azim
通讯作者：
Surani, M. Azim