When the SWI/SNF complex remodels...the cell cycle.
Mammalian cells contain several chromatin-remodeling complexes associated with the Brm and Brg1 helicase-like proteins. These complexes likely represent the functional homologs of the SWI/SNF and RSC complexes found in Saccharomyces cerevisiae. The mammalian chromatin-remodeling complexes are involved in both activation and repression of a variety of genes. Several lines of evidence also indicate that they play a specific role in the regulation of cell growth. Brm is down-regulated by ras signaling and its forced re-expression suppresses transformation by this oncogene. Besides, the Brg1 gene is silenced or mutated in several tumors cell lines and a Brg1-associated complex was recently found to co-purify with BRCA1, involved in breast and ovarian cancers. Finally, the gene encoding SNF5/Ini1, a subunit common to all mammalian SWI/SNF complexes, is inactivated in rhabdoid sarcomas, a very aggressive form of pediatric cancer. The current review will address observations made upon inactivation of Brm, Brg1 and SNF5/Ini1 by homologous recombination in the mouse, as well as the possible implication of these factors in the regulation of the Retinoblastoma pRb-mediated repression of the transcription factor E2F.
Muchardt
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Unité des Virus Oncogènes, URA1644 du CNRS, Département des Biotechnologies, Institut Pasteur, Paris, France.
Yaniv
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D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases