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Publication : MyoD synergizes with the E-protein HEB beta to induce myogenic differentiation.

First Author  Parker MH Year  2006
Journal  Mol Cell Biol Volume  26
Issue  15 Pages  5771-83
PubMed ID  16847330 Mgi Jnum  J:111413
Mgi Id  MGI:3653966 Doi  10.1128/MCB.02404-05
Citation  Parker MH, et al. (2006) MyoD synergizes with the E-protein HEB beta to induce myogenic differentiation. Mol Cell Biol 26(15):5771-83
abstractText  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 alpha and beta 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 HEB alpha expression remains unchanged in both myoblasts and myotubes, whereas HEB beta is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEB beta complex bound the E1 E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEB beta with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEB alpha and HEB beta synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEB beta by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEB alpha and HEB beta play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation.
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