Selective utilization of basic helix-loop-helix-leucine zipper proteins at the immunoglobulin heavy-chain enhancer.
The microE3 E box within the immunoglobulin heavy-chain (IgH) enhancer binds several proteins of the basic helix-loop-helix-leucine zipper (bHLHzip) class, including TFE3, USF1, and Max. Both TFE3 and USF have been described as transcriptional activators, and so we investigated their possible roles in activating the IgH enhancer in vivo. Although TFE3 activated various enhancer-based reporters, both USF1 and Max effectively inhibited transcription. Inhibition by USF correlated with the lack of a strong activation domain and was the result of the protein neutralizing the microE3 site. The effects of dominant-negative derivatives of TFE3 and USF1 confirmed that TFE3, or a TFE3-like protein, is the primary cellular bHLHzip protein that activates the IgH enhancer. In addition to providing a physiological role for TFE3, our results call into question the traditional view of USF1 as an obligate transcriptional activator.
Carter
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RS
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6145, USA.
Ordentlich
P
P
Kadesch
T
T
D016475:3T3 Cells; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016350:Leucine Zippers; D051379:Mice; D009154:Mutation; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; C067850:Myc associated factor X; D011993:Recombinant Fusion Proteins; C069203:TFE3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C068422:Max protein, mouse