RESEARCH ARTICLE Polycomb Protein SCML2 Associates with

Polycomb group proteins mediate transcriptional silencing in diverse developmental pro-cesses. Sex chromosomes undergo chromosome-wide transcription silencing during male meiosis. Here we report that mouse SCML2 (Sex comb on midleg-like 2), an X chromo-some-encoded polycomb protein, is specifically expressed in germ cells, including sper-matogonia, spermatocytes, and round spermatids. SCML2 associates with phosphorylated H2AX and localizes to the XY body in spermatocytes. Loss of SCML2 in mice causes defec-tive 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 dra-matically 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. Author Summary Chromatin-modifying enzymes regulate the chromatin state during development and dis