Open AccessMyoD Synergizes with the E-Protein HEBβ To Induce Myogenic Differentiation
Author(s) -
Maura H. Parker,
Robert L. Perry,
Mélanie C Fauteux,
Charlotte A. Berkes,
Michael A. Rudnicki
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.02404-05
Subject(s) - myogenin , myod , myogenesis , biology , myod protein , myocyte , microbiology and biotechnology , transcription factor , cellular differentiation , myogenic regulatory factors , gene isoform , genetics , gene
The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate α and β isoforms. While the function of these molecules has been studied in other cell types, questions persist regarding the molecular functions of HEB proteins in skeletal muscle. Our data demonstrate that HEBα expression remains unchanged in both myoblasts and myotubes, whereas HEBβ is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEBβ complex bound the E1 E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEBβ with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEBα and HEBβ synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEBβ by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEBα and HEBβ play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation.