title: The Polycomb Repressive Complex 1 Protein BMI1 Is Required for Constitutive Heterochromatin Formation and Silencing in Mammalian Somatic Cells.
abstract: The polycomb repressive complex 1 (PRC1), containing the core BMI1 and RING1A/B proteins, mono-ubiquitinylates histone H2A (H2A(ub)) and is associated with silenced developmental genes at facultative heterochromatin. It is, however, assumed that the PRC1 is excluded from constitutive heterochromatin in somatic cells based on work performed on mouse embryonic stem cells and oocytes. We show here that BMI1 is required for constitutive heterochromatin formation and silencing in human and mouse somatic cells. BMI1 was highly enriched at intergenic and pericentric heterochromatin, co-immunoprecipitated with the architectural heterochromatin proteins HP1, DEK1, and ATRx, and was required for their localization. In contrast, BRCA1 localization was BMI1-independent and partially redundant with that of BMI1 for H2A(ub) deposition, constitutive heterochromatin formation, and silencing. These observations suggest a dynamic and developmentally regulated model of PRC1 occupancy at constitutive heterochromatin, and where BMI1 function in somatic cells is to stabilize the repetitive genome.
authors.affiliation: From the Department of Neurosciences, University of Montreal, and The Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal H1T 2M4, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdouh
authors.affiliation: From the Department of Neurosciences, University of Montreal, and The Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal H1T 2M4, Canada.
authors.forename: Roy
authors.initials: R
authors.lastname: Hanna
authors.affiliation: From the Department of Neurosciences, University of Montreal, and The Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal H1T 2M4, Canada.
authors.forename: Jida
authors.initials: J
authors.lastname: El Hajjar
authors.affiliation: From the Department of Neurosciences, University of Montreal, and The Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal H1T 2M4, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Flamier
authors.affiliation: From the Department of Neurosciences, University of Montreal, and The Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal H1T 2M4, Canada gbernier.hmr@ssss.gouv.qc.ca.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bernier
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000172:deficiency / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D019313:BRCA1 Protein; C489421:Bmi1 protein, mouse; D006570:Heterochromatin; D006657:Histones; D011518:Proto-Oncogene Proteins; D025801:Ubiquitin; D063150:Polycomb Repressive Complex 1
keywords: BMI1; BRCA1; heterochromatin; histone H2A; lamin; polycomb; ubiquitylation (ubiquitination)