The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.
We have isolated a cDNA clone encoding a novel helix-loop-helix (HLH) protein, Id. Id is missing the basic region adjacent to the HLH domain that is essential for specific DNA binding in another HLH protein, MyoD. An in vitro translation product of Id can associate specifically with at least three HLH proteins (MyoD, E12, and E47) and attenuate their ability to bind DNA as homodimeric or heterodimeric complexes. Id is expressed at varying levels in all cell lines tested. In three cell lines that can be induced to undergo terminal differentiation, Id RNA levels decrease upon induction. Transfection experiments indicate that over-expression of Id inhibits the trans-activation of the muscle creatine kinase enhancer by MyoD. Based on these findings, we propose that HLH proteins lacking a basic region may negatively regulate other HLH proteins through the formation of nonfunctional heterodimeric complexes.
Benezra
R
R
Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Davis
R L
RL
Lockshon
D
D
Turner
D L
DL
Weintraub
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003402:Creatine Kinase / Q000235:genetics; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015723:Gene Library; D005809:Genes, Regulator; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000201:enzymology; D017570:MyoD Protein; D015345:Oligonucleotide Probes; D012097:Repressor Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D014162:Transfection
D015342:DNA Probes; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009124:Muscle Proteins; D017570:MyoD Protein; D015345:Oligonucleotide Probes; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D003402:Creatine Kinase