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 from the IgH intronic enhancer (E mu). We show here that Bright has multiple contextual requirements to function as a transcriptional activator. Bright cannot transactivate via out of context, concatenated binding sites. Transactivation is maximal on integrated substrates. Two of the three previously identified binding sites in E mu are required for full Bright transactivation. 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 box proteins, Bright distorts E mu binding site-containing DNA on binding, supporting the concept that it mediates E mu remodeling. Transfection studies further implicate Bright in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays. Finally, we show that overexpression of Bright leads to enhanced DNase I sensitivity of the endogenous E mu matrix associating regions. These data further suggest that Bright may contribute to increased gene expression by remodeling the immunoglobulin locus during B cell development.
Kaplan
M H
MH
Institute for Molecular and Cellular Biology, University of Texas at Austin, Austin, Texas 78712-1075, USA.
Zong
R T
RT
Herrscher
R F
RF
Scheuermann
R H
RH
Tucker
P W
PW
D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I; D029721:Drosophila Proteins; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D009857:Oncogenes; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
C490798:ARID3A protein, human; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007143:Immunoglobulin Heavy Chains; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; C089969:snf protein, Drosophila; D015500:Chloramphenicol O-Acetyltransferase; D003850:Deoxyribonuclease I