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Genes 2011, 2(1), 59-80; doi:10.3390/genes2010059
Article

Role of Polycomb Group Protein Cbx2/M33 in Meiosis Onset and Maintenance of Chromosome Stability in the Mammalian Germline

1,2
 and 1,2,*
Received: 30 November 2010; in revised form: 16 December 2010 / Accepted: 6 January 2011 / Published: 11 January 2011
(This article belongs to the Special Issue Genetics of Mammalian Meiosis)
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Abstract: 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 gH2AX 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.
Keywords: oogenesis; pericentric heterochromatin; epigenetic modifications; chromatin remodeling; retinoic acid; sex determination oogenesis; pericentric heterochromatin; epigenetic modifications; chromatin remodeling; retinoic acid; sex determination
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Baumann, C.; De La Fuente, R. Role of Polycomb Group Protein Cbx2/M33 in Meiosis Onset and Maintenance of Chromosome Stability in the Mammalian Germline. Genes 2011, 2, 59-80.

AMA Style

Baumann C, De La Fuente R. Role of Polycomb Group Protein Cbx2/M33 in Meiosis Onset and Maintenance of Chromosome Stability in the Mammalian Germline. Genes. 2011; 2(1):59-80.

Chicago/Turabian Style

Baumann, Claudia; De La Fuente, Rabindranath. 2011. "Role of Polycomb Group Protein Cbx2/M33 in Meiosis Onset and Maintenance of Chromosome Stability in the Mammalian Germline." Genes 2, no. 1: 59-80.



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