B-cell-specific DNA binding by an E47 homodimer.
B cells express a unique E-box-binding activity that contains basic helix-loop-helix (bHLH) proteins encoded by the E2A gene. E2A proteins play a central role in immunoglobulin gene transcription and are also required for the generation of the B-lymphocyte lineage. In muscle, E2A proteins bind DNA as heterodimers with muscle-specific bHLH partners, such as MyoD and myogenin, and these heterodimers are thought to be both necessary and sufficient for muscle determination in cultured cells. Our results indicate that in B cells, the bHLH partners for E2A proteins are not B-cell-restricted proteins, but are the E2A proteins themselves. UV cross-linking, gel purification, and the analysis of "forced heterodimers" indicate that BCF1 is primarily a homodimer of the E2A protein E47. Since E47 is widely expressed, our results argue for a difference in the inherent DNA-binding properties of the E47 protein in B cells and may help explain the restricted B-lineage defect observed in E2A-deficient mice.
Shen
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Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Kadesch
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D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012326:RNA Splicing; D051820:TCF Transcription Factors; D014018:Tissue Distribution; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors