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Polycomb Protein SCML2 Associates with USP7 and Counteracts Histone H2A Ubiquitination in the XY Chromatin 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.


Vyšlo v časopise: Polycomb Protein SCML2 Associates with USP7 and Counteracts Histone H2A Ubiquitination in the XY Chromatin during Male Meiosis. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004954
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004954

Souhrn

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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