title: Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis.
abstract: 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.
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Mengcheng
authors: M
authors: Luo
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Jian
authors: J
authors: Zhou
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: N Adrian
authors: NA
authors: Leu
authors: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors: Carla M
authors: CM
authors: Abreu
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Jianle
authors: J
authors: Wang
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Montserrat C
authors: MC
authors: Anguera
authors: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Dirk G
authors: DG
authors: de Rooij
authors: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors: Maria
authors: M
authors: Jasin
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: P Jeremy
authors: PJ
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D020868:Gene Silencing; D006657:Histones / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000254:growth & development / Q000378:metabolism; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D046912:Multiprotein Complexes; D063146:Polycomb-Group Proteins; C000600067:SCML2 protein, mouse; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C579190:Usp7 protein, mouse
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