Transcriptional activation by a matrix associating region-binding protein - Contextual requirements for the function of Bright

Bright (B cell regulator of IgH transcription) is a B cell-specific, matrix associating region-binding protein that transactivates gene expression fro m the IgH intronic enhancer (E mu). We show here that Bright has multiple c ontextual requirements to function as a transcriptional activator. Bright c annot transactivate via out of context, concatenated binding sites. Transac tivation is maximal on integrated substrates. Two of: the three previously identified binding sites in E mu are required for full Bright transactivati on, The Bright DNA binding domain defined a new family, which includes SWI1 , a component of the SWI.SNF complex shown to have high mobility group-like DNA binding characteristics. Similar to one group of high mobility group b ox proteins, Bright distorts E mu binding site-containing DNA on binding, s upporting the concept that it mediates E mu remodeling. Transfection studie s further implicate Bright in facilitating spatially separated promoter-enh ancer interactions in both transient and stable assays. Finally, we show th at overexpression of Bright leads to enhanced DNase I sensitivity of the en dogenous E mu matrix associating regions. These data further suggest that B right may contribute to increased gene expression by remodeling the immunog lobulin locus during B cell development.