The c-myc gene is a direct target of mammalian SWI/SNF-related complexes during differentiation-associated cell cycle arrest.
The activity of mammalian SWI/SNF-related chromatin remodeling complexes is crucial for differentiation, development, and tumor suppression. Cell cycle-regulating activities dependent on the complexes include induction of the p21(WAF1/CIP1) kinase inhibitor and repression of E2F-responsive promoters. These responses are linked through effects on pRb phosphorylation, but the direct role of the SWI/SNF-related complexes in their regulation is not fully understood. Results presented here reveal that the complexes are required for regulation of a distinct pathway of proliferation control involving repression of c-myc expression in differentiating cells. This involves direct promoter targeting of the c-myc gene by the complexes. Induction of p21(WAF1/CIP1) is specifically dependent on prior repression of c-myc, but repression of E2F-responsive genes is dissociable from the regulation of c-myc and p21(WAF1/CIP1).
Nagl
Norman G
NG
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Zweitzig
Daniel R
DR
Thimmapaya
Bayar
B
Beck
George R
GR
Moran
Elizabeth
E
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency; D050684:E2F Transcription Factors / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D016259:Genes, myc / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*
C497837:ARID1B protein, human; C511511:Arid1a protein, mouse; C493957:Cdkn1a protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors