An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers.
The kappa E2 sequence binding proteins, E12 and E47, are generated by alternative splicing of the E2A gene, giving closely related basic and helix-loop-helix structures crucial for DNA binding and dimerization. Measurements of dimerization constants and binding strengths to the optimal DNA sequence (the kappa E2 site or its near relatives) showed that E47 homodimers and MyoD heterodimers with E12 or E47 dimerized and bound avidly, but E12 homodimerized efficiently and bound to DNA poorly; MyoD homodimerized poorly and bound strongly. An inhibitory domain N-terminal to the basic region of E12 prevents E12 homodimers but not E12/MyoD heterodimers from binding to DNA. Thus, E47 binds to DNA both as a heterodimer with MyoD and as a homodimer, while E12 and MyoD bind to DNA efficiently only as heterodimers.
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005091:Exons; D015723:Gene Library; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D017570:MyoD Protein; D015345:Oligonucleotide Probes; D011485:Protein Binding; D011487:Protein Conformation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009124:Muscle Proteins; D017570:MyoD Protein; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA