论文信息 - HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.

HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.

Proteins containing the basic-helix-loop-helix (B-HLH) domain have been shown to be important in regulating cellular differentiation. We have isolated a cDNA for a human B-HLH factor, denoted HEB, that shares nearly complete identity in the B-HLH domain with the immunoglobulin enhancer binding proteins encoded by the E2A and ITF2 genes (E proteins). Functional characterization of the protein expressed from this cDNA indicates that HEB is a third member of the E-protein class of B-HLH factors. HEB mRNA was found to be expressed in several tissues and cell types, including skeletal muscle, thymus, and a B-cell line. HEB, ITF2, and the E12 product of the E2A gene all bound to a similar spectrum of E-box sequences as homo-oligomers. All three factors also formed hetero-oligomers with myogenin, and the DNA-binding specificity and binding off-rates (dissociation rates) were modulated after hetero-oligomerization. Both homo- and hetero-oligomers of these proteins were able to distinguish between very closely related E-box sequences. In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins. Finally, HEB was able to activate gene expression. These data demonstrate that HEB shares characteristics with other E proteins and show that HEB can interact with members of both the myogenic regulatory class and the E-protein class of B-HLH factors. HEB is therefore likely to play an important role in regulating lineage-specific gene expression.

R. Kingston | E. Olson | J. Hu

[1] A. Feinberg,et al. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[2] S. Rhodes,et al. Identification of MRF4: a new member of the muscle regulatory factor gene family. , 1989, Genes & development.

[3] Y. Jan,et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence , 1989, Cell.

[4] D. Baltimore,et al. Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[5] P. Sharp,et al. HTF4: a new human helix-loop-helix protein. , 1991, Nucleic acids research.

[6] K. Yutzey,et al. Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors , 1991, Molecular and cellular biology.