title: USP7 cooperates with SCML2 to regulate the activity of PRC1.
abstract: USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of Polycomb repressive complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes. Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive activity. USP7 regulates the posttranslational status of RING1B and BMI1, a specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components, its catalytic activity is also necessary to maintain a functional PRC1, thereby ensuring appropriate levels of repressive H2Aub.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, USA.
authors.forename: Emilio
authors.initials: E
authors.lastname: Lecona
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Narendra
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, USA Danny.Reinberg@nyumc.org.
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D002460:Cell Line; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: D063146:Polycomb-Group Proteins; C119751:SCML2 protein, human; D063150:Polycomb Repressive Complex 1; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7