Distinct mammalian SWI/SNF chromatin remodeling complexes with opposing roles in cell-cycle control.
The mammalian SWI/SNF chromatin remodeling complex is becoming increasingly recognized for its role in tumor suppression, based on its ability to regulate accessibility of proliferation-associated genes to transcription factors. However, understanding the biological role of the complex is complicated because the same complex seemingly plays both positive and negative roles in gene expression. Work described here reveals that a choice between two independently encoded, closely related variants of a major subunit of the ARID protein family determines whether the SWI/SNF complex forms further associations with activator versus repressor complexes. The choice distinguishes assemblies with opposite effects on cell-cycle activity. The specific complexes control access of factors such as E2F1, Tip60, and HDAC1/2/3 to the promoters of various cell-cycle-specific genes, with c-Myc emerging as a particularly critical target.
Nagl
Norman G
NG
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Wang
Xiaomei
X
Patsialou
Antonia
A
Van Scoy
Michael
M
Moran
Elizabeth
E
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D016259:Genes, myc / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C511511:Arid1a protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D021122:Protein Subunits; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases