Volume 272, Number 32, Issue of August 8, 1997 pp. 19785-19793
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Interactions of Id Proteins with Basic-Helix-Loop-Helix Transcription Factors

(Received for publication, March 21, 1997, and in revised form, June 5, 1997)

Kenneth Langlands , Xiaoying Yin , Geetha Anand and Edward V. Prochownik ^§¶

From the  Section of Hematology/Oncology, Children's Hospital of Pittsburgh, The ^§ Department of Molecular Genetics and Biochemistry, and ^¶ The University of Pittsburgh Cancer Institute, The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213

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.

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