Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
A DNA binding and dimerization motif, with apparent amphipathic helices (the HLH motif), has recently been identified in various proteins, including two that bind to immunoglobulin enhancers (E12 and E47). We show here that various HLH proteins can bind as apparent heterodimers to a single DNA motif and also, albeit usually more weakly, as apparent homodimers. The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 (Class A) and achaete-scute T3 or MyoD (Class B) to form proteins with high affinity for the kappa E2 site in the immunoglobulin kappa chain enhancer. The achaete-scute T3 and MyoD proteins do not form kappa E2-binding heterodimers together, and no active complex with N-myc was evident. The formation of a heterodimer between the daughterless and achaete-scute T3 products may explain the similar phenotypes of mutants at these two loci and the genetic interactions between them. A role of E12 and E47 in mammalian development, analogous to that of daughterless in Drosophila, is likely.
Murre
C
C
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
McCaw
P S
PS
Vaessin
H
H
Caudy
M
M
Jan
L Y
LY
Jan
Y N
YN
Cabrera
C V
CV
Buskin
J N
JN
Hauschka
S D
SD
Lassar
A B
AB
D000818:Animals; D001665:Binding Sites; D003402:Creatine Kinase / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D004331:Drosophila melanogaster / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D046911:Macromolecular Substances; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D014157:Transcription Factors; D004247:DNA; D003402:Creatine Kinase