Exploring functional redundancy in the immunoglobulin mu heavy-chain gene enhancer.
Immunoglobulin (Ig) mu heavy-chain gene enhancer activity is mediated by multiple DNA binding proteins. Mutations of several protein binding sites in the enhancer do not affect enhancer activity significantly. This feature, termed redundancy, is thought to be due to functional compensation of the mutated sites by other elements within the enhancer. In this study, we identified the elements that make the basic helix-loop-helix (bHLH) protein binding sites, muE2 and muE3, redundant. The major compensatory element is a binding site for interferon regulatory factors (IRFs) and not one of several other bHLH protein binding sites. These studies also provide the first evidence for a role of IRF proteins in Ig heavy-chain gene expression. In addition, we reconstituted the activity of a monomeric mu enhancer in nonlymphoid cells and defined the domains of the ETS gene required for function.
Rosenstiel Research Center and Departments of Biology and Biochemistry, Brandeis University, Waltham, Massachusetts 02254, USA.
W
W
Dang
B S
BS
Nikolajczyk
R
R
Sen
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D007148:Immunoglobulin mu-Chains; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D007372:Interferons