Inventors:
C. M. Amy Chen - Brookline MA
Norbert Kraut - Seattle WA
Mark Groudine - Seattle WA
Harold Weintraub - late of Seattle WA
Assignee:
Fred Hutchinson Cancer Research Center - Seattle WA
International Classification:
C12P 2106
Abstract:
A novel gene, Inhibitor of MyoD Family (I-mf), is provided which encodes novel proteins, I-mfa, I-mfb and I-mfc, involved in regulation of myogenesis during vertebrate development. I-mf is highly expressed in the sclerotome of developing vertebrates and is postulated to play an important role in patterning of the somite and determination sclerotomal cell fate. A unique, C-terminal interactional domain of the I-mf protein mediates physical interactions between I-mfa and members of the MyoD family of transcriptional activators and functions to inhibit transactivation of muscle specific genes by MyoD family members, thereby repressing myogenesis. Further characterization of I-mf activity shows that I-mf associates with MyoD family member proteins and retains them in the cytoplasm by masking their nuclear localization signals. Based on the I-mf genes and proteins disclosed herein, a variety methods and compositions are provided for screening, isolating, and characterizing endogenous and exogenous factors, drugs and therapeutic agents useful to evaluate and/or control myogenesis normal and abnormal development and cell differentiation.