Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization

Cell Reports

Timo Zimmermann¹  Manel Esteller²  Miguel Vizoso²  Juan Ausió³  Antonio Gómez⁴  Alejandro Vaquero⁵  Jessica González⁵  Laia Bosch-Presegué⁵  Helena Raurell-Vila⁵  Noriko Kane-Goldsmith⁶  Lourdes Serrano⁶  Joshua K. Thackray⁶  Prim B. Singh⁷  Jeremy P. Brown⁷  Gunnar Schotta⁸  Carmen Casal⁹ 

[1] Advanced Light Microscopy Unit, Center for Genomic Regulation, C/ Dr. Aiguader 88, 08003 Barcelona, Spain;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;Center for Biomedical Research, University of Victoria, Victoria, BC V8W 3N5, Canada;Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain;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;Department of Genetics, Human Genetics Institute, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA;Fächerverbund Anatomie, Institut für Zell-und Neurobiologie, Charite-Universitätsmedizin, 10117 Berlin, Germany;Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPSM), Biomedical Center, Planegg-Martinsried, Germany;Microcopy Unit, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l’Hospitalet, 199-203, 08908- L’Hospitalet de Llobregat, Barcelona, Spain;

关键词: heterochromatin;    HP1α;    HP1β;    HP1γ;    Suv420h2;    H4K20me3;    heterochromatin;    genome organization;    genome stability;   

DOI  :  10.1016/j.celrep.2017.10.092

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown