Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization
Laia Bosch-Presegué,
Helena Raurell-Vila,
Joshua K. Thackray,
Jessica González,
Carmen Casal,
Noriko Kane-Goldsmith,
Miguel Vizoso,
Jeremy P. Brown,
Antonio Gómez,
Juan Ausió,
Timo Zimmermann,
Manel Esteller,
Gunnar Schotta,
Prim B. Singh,
Lourdes Serrano,
Alejandro Vaquero
Affiliations
Laia Bosch-Presegué
Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08907- L’Hospitalet de Llobregat, Barcelona, Spain
Helena Raurell-Vila
Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08907- L’Hospitalet de Llobregat, Barcelona, Spain
Joshua K. Thackray
Department of Genetics, Human Genetics Institute, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA
Jessica González
Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08907- L’Hospitalet de Llobregat, Barcelona, Spain
Carmen Casal
Microcopy Unit, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08908- L’Hospitalet de Llobregat, Barcelona, Spain
Noriko Kane-Goldsmith
Department of Genetics, Human Genetics Institute, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA
Miguel Vizoso
Cancer Epigenetics Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08908- L’Hospitalet de Llobregat, Barcelona, Spain
Jeremy P. Brown
Fächerverbund Anatomie, Institut für Zell-und Neurobiologie, Charite-Universitätsmedizin, 10117 Berlin, Germany
Antonio Gómez
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain
Juan Ausió
Center for Biomedical Research, University of Victoria, Victoria, BC V8W 3N5, Canada
Timo Zimmermann
Advanced Light Microscopy Unit, Center for Genomic Regulation, C/ Dr. Aiguader 88, 08003 Barcelona, Spain
Manel Esteller
Cancer Epigenetics Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08908- L’Hospitalet de Llobregat, Barcelona, Spain
Gunnar Schotta
Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPSM), Biomedical Center, Planegg-Martinsried, Germany
Prim B. Singh
Fächerverbund Anatomie, Institut für Zell-und Neurobiologie, Charite-Universitätsmedizin, 10117 Berlin, Germany
Lourdes Serrano
Department of Genetics, Human Genetics Institute, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA
Alejandro Vaquero
Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08907- L’Hospitalet de Llobregat, Barcelona, Spain
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α−/−, Hp1β−/−, and Hp1γ−/− MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects. In contrast, HP1β is functionally associated with Suv4-20h2 and H4K20me3, and its loss induces global chromatin decompaction and an abnormal enrichment of CTCF in PCH and other genomic regions. Our work provides insight into the roles of HP1 proteins in heterochromatin structure and genome stability.
