title: Differential interactions of Id proteins with basic-helix-loop-helix transcription factors.
abstract: Dimerization of three Id proteins (Id1, Id2, and Id3) with the four class A E proteins (E12, E47, E2-2, and HEB) and two groups of class B proteins, the myogenic regulatory factors (MRFs: MyoD, myogenin, Myf-5 and MRF4/Myf-6), and the hematopoietic factors (Scl/Tal-1, Tal-2, and Lyl-1) were tested in a quantitative yeast 2-hybrid assay. All three Ids bound with high affinity to E proteins, but a much broader range of interactions was observed between Ids and the class B factors. Id1 and Id2 interacted strongly with MyoD and Myf-5 and weakly with myogenin and MRF4/Myf-6, whereas Id3 interacted weakly with all four MRFs. Similar specificities were observed in co-immunoprecipitation and mammalian 2-hybrid analyses. No interactions were found between the Ids and any of the hematopoietic factors. Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. Finally, mutagenesis experiments showed that the differences between Id1 and Id3 binding map to three amino acids in the first helix and to a small cluster of upstream residues. The Id proteins thus display a signature range of interactions with all of their potential dimerization partners and may play a role in myogenesis which is distinct from that in hematopoiesis.
authors.affiliation: Section of Hematology/Oncology, Children's Hospital of Pittsburgh, The, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: K
authors.initials: K
authors.lastname: Langlands
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.forename: G
authors.initials: G
authors.lastname: Anand
authors.forename: E V
authors.initials: EV
authors.lastname: Prochownik
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D000073940:Transcription Factor 4; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D009124:Muscle Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D000073940:Transcription Factor 4; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C497455:Idb1 protein, mouse; C503799:MYOG protein, human; C497418:Myf5 protein, mouse; C503801:Myog protein, mouse; C544912:TCF7L1 protein, human; C489532:Tcf12 protein, mouse; C090743:Tcf4 protein, mouse; C544913:Tcf7l1 protein, mouse; C063403:myogenic factor 6; C073366:TCF12 protein, human