Title

MyoD can induce cell cycle arrest but not muscle differentiation in the presence of dominant negative SWI/SNF chromatin remodeling enzymes

UMMS Affiliation

Department of Cell Biology

Date

8-28-2001

Document Type

Article

Subjects

Base Sequence; Cell Cycle; Cell Differentiation; Cells, Cultured; Chromatin; Cyclins; DNA Primers; Muscle, Skeletal; MyoD Protein; Oncogene Protein p21(ras); Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

Cell cycle arrest is critical for muscle differentiation, and the two processes are closely coordinated but temporally separable. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that have been shown to be required for muscle differentiation in cell culture and have also been reported to be required for Rb-mediated cell cycle arrest. We therefore looked more closely at how SWI/SNF enzymes affect the events that occur during MyoD-induced myogenesis, namely, cell cycle regulation and muscle-specific gene expression, in cells that inducibly express dominant negative versions of Brahma (BRM) and Brahma-related gene 1 (BRG1), the ATPase subunits of two distinct SWI/SNF complexes. Although dominant negative BRM and BRG1 inhibited expression of every muscle-specific regulator and structural gene assayed, there was no effect on MyoD-induced activation of cell cycle regulatory proteins, and thus, cells arrested normally. In particular, in the presence or absence of dominant negative BRM or BRG1, MyoD was able to activate expression of p21, cyclin D3, and Rb, all of which are critical for cell cycle withdrawal in the G1/G0 phase of the cell cycle. These findings suggest that at least one basis for the distinct mechanisms that regulate cessation of cell proliferation and muscle-specific gene expression during muscle differentiation is that SWI/SNF-mediated chromatin-remodeling enzymes are required only for the latter.

Rights and Permissions

Citation: J Biol Chem. 2001 Nov 2;276(44):41486-91. Epub 2001 Aug 24. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M107281200

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

11522799