The ATP-dependent chromatin-remodeling complexes play important roles in gene regulation by opening chromatin structures for transcriptional activators or repressors. The prototype of this type of complexes is the SWI/SNF complex, which was found from diverse organisms, including yeast, Drosophila, mouse and human. It is required for proper expression of homeotic genes and segmentation in Drosophila. Mutation in one subunit of the complex causes pediatric rhabdoid cancer in human. I have purified several human SWI/SNF-related complexes previously at Stanford. By microsequencing, my colleagues and I have identified and cloned most of the subunits from the major form of the complex. In the continuation of this project, we have microsequenced and cloned its largest subunit, BAF250. Sequence analysis revealed that BAF250 contains a DNA binding domain similar to yeast SWI1, and several LXXLL motifs which have been previously shown to be able to interact nuclear hormone receptors. Using transient transfection assays, we found that BAF250 facilitates transcriptional activation by glucocorticoid receptor (GR). The region containing LXXLL motifs of BAF250 also interacts with GR in vitro. This work suggests that BAF250 may be a targeting subunit of hSWI/SNF, and may mediate the recruitment of the complex to DNA-bound glucocorticoid receptors. - Chromatin, SWI/SNF, BAF250, transcription
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