Mutually exclusive interaction of a novel matrix attachment region binding protein and the NF-muNR enhancer repressor. Implications for regulation of immunoglobulin heavy chain expression.
The immunoglobulin heavy chain (IgH) intronic enhancer stimulates transcription from functional promoters in B lymphocytes but not other cell types. The observation that binding sites for the nuclear factor-mu negative regulator (NF-muNR) enhancer repressor overlap nuclear matrix attachment regions (MARs) in this enhancer has lead to the hypothesis that the cell type specificity of the enhancer might be controlled by regulating nuclear matrix attachment (Scheuermann, R. H., and Chen, U. (1989) Genes & Dev. 3, 1255-1266). To understand the role of MARs in IgH enhancer regulation, we have identified a novel MAR-binding protein, MAR-BP1, from soluble nuclear matrix preparations based on its ability to bind to the MARs associated with the IgH enhancer. Purified MAR-BP1 migrates as a 33-kDa protein, and it can be found in nuclear matrix preparations from a number of different types of lymphoid cell lines. Although specific binding sites have been difficult to localize by chemical or enzymatic footprinting procedures, NF-muNR binding sites are critical for efficient MAR-BP1 binding. Indeed, binding of the IgH enhancer to either intact nuclear matrix preparations or to MAR-BP1 is mutually exclusive to NF-muNR binding. These results are consistent with a model for cell-type specific regulation in which binding of the NF-muNR repressor to the IgH enhancer prevents nuclear matrix attachment in inappropriate cells by interfering with MAR-BP1/enhancer interaction.
Zong
R T
RT
Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
Scheuermann
R H
RH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics*; D007438:Introns; D007700:Kinetics; D008961:Models, Structural; D015530:Nuclear Matrix / Q000378:metabolism*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D012097:Repressor Proteins / Q000378:metabolism*; D015183:Restriction Mapping
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D012097:Repressor Proteins