SWI/SNF deficiency results in aberrant chromatin organization, mitotic failure, and diminished proliferative capacity.: SWI/SNF Deficiency Causes Failed Mitosis

Autor: Bourgo, Ryan, Siddiqui, Hasan, Fox, Sejal, Solomon, David, Sansam, Courtney, Yaniv, Moshe, Muchardt, Christian, Metzger, Daniel, Chambon, Pierre, Roberts, Charles, Knudsen, Erik
Přispěvatelé: Department of Cancer Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Human Cancer Genetics Program, Comprehensive Cancer Center-College of Medicine and Public Health [Colombus], Department of Cell and Cancer Biology, University of Cincinnati (UC), Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Department of Pediatric Oncology, Dana-Farber Cancer Institute [Boston], Expression Génétique et Maladies (EGM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, E.S.K. is supported by National Cancer Institute grant CA 104213., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Molecular Biology of the Cell
Molecular Biology of the Cell, American Society for Cell Biology, 2009, 20 (14), pp.3192-9. ⟨10.1091/mbc.E08-12-1224⟩
Molecular Biology of the Cell, 2009, 20 (14), pp.3192-9. ⟨10.1091/mbc.E08-12-1224⟩
ISSN: 1939-4586
DOI: 10.1091/mbc.E08-12-1224⟩
Popis: International audience; Switch (SWI)/sucrose nonfermentable (SNF) is an evolutionarily conserved complex with ATPase function, capable of regulating nucleosome position to alter transcriptional programs within the cell. It is known that the SWI/SNF complex is responsible for regulation of many genes involved in cell cycle control and proliferation, and it has recently been implicated in cancer development. The ATPase action of SWI/SNF is conferred through either the brahma-related gene 1 (Brg1) or brahma (Brm) subunit of the complex, and it is of central importance to the modification of nucleosome position. In this study, the role of the Brg1 and Brm subunits were examined as they relate to chromatin structure and organization. Deletion of the Brg1 ATPase results in dissolution of pericentromeric heterochromatin domains and a redistribution of histone modifications associated with these structures. This effect was highly specific to Brg1 and is not reproduced by the loss of Brm or SNF5/BAF47/INI1. Brg1 deficiency is associated with the appearance of micronuclei and aberrant mitoses that are a by-product of dissociated chromatin structure. Thus, Brg1 plays a critical role in maintaining chromatin structural integrity.
Databáze: OpenAIRE
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