The activity of mammalian brm/SNF2alpha is dependent on a high-mobility-group protein I/Y-like DNA binding domain.
The mammalian SWI-SNF complex is a chromatin-remodelling machinery involved in the modulation of gene expression. Its activity relies on two closely related ATPases known as brm/SNF2alpha and BRG-1/SNF2beta. These two proteins can cooperate with nuclear receptors for transcriptional activation. In addition, they are involved in the control of cell proliferation, most probably by facilitating p105(Rb) repression of E2F transcriptional activity. In the present study, we have examined the ability of various brm/SNF2alpha deletion mutants to reverse the transformed phenotype of ras-transformed fibroblasts. Deletions within the p105(Rb) LXCXE binding motif or the conserved bromodomain had only a moderate effect. On the other hand, a 49-amino-acid segment, rich in lysines and arginines and located immediately downstream of the p105(Rb) interaction domain, appeared to be essential in this assay. This region was also required for cooperation of brm/SNF2alpha with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome. The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2alpha to chromatin.
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000502:physiology; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002843:Chromatin / Q000502:physiology; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D017930:Genes, Reporter; D008239:Lysine / Q000502:physiology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019913:Nuclear Localization Signals / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D010957:Plasmids; D011965:Receptors, Glucocorticoid / Q000235:genetics; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection