The c-myc Gene Is a Direct Target of Mammalian SWI/SNF–Related Complexes during Differentiation-Associated Cell Cycle Arrest

Abstract

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. (Cancer Res 2006; 66(3): 1289-93)