P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation

Sheng P. Hsiao, Kai M. Huang, Hsin Y. Chang, Shen L. Chen

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18 Scopus citations


Previously, we found that MRFs (myogenic regulatory factors) regulated the expression of PGC-Iα (peroxisome-proliferator-activated receptor γ co-activator 1α) by targeting a short region, from nt - 49 to + 2 adjacent to the transcription initiation site, that contained two E-boxes. However, only the E2-box had significant affinity for MRFs, and the E1-box was predicted to be the target of Bhlhe40 (basic helix-loop-helix family, member e40, also known as Stra13, Bhthb2, DEC1 and Sharp2), a transcriptional repressor implicated in the regulation of several physiological processes. In the present study, by using EMSA (electrophoresis mobility-shift assay), we confirmed that Bhlhe40 targeted the E1-box and formed a complex with the basic helix-loop-helix transcription factor MyoD (myogenic differentiation factor D) on the PGC-1α core promoter. We demonstrate that Bhlhe40 binds to the promoters of PGC-1α and myogenic genes in vivo and that Bhlhe40 represses the MyoD-mediated transactivation of these promoters. Furthermore, we found that this repression could be relieved by P/CAF (p300/CBP-associated factor) in a dose-dependent manner, but not by CBP [CREB (cAMP-response-element-binding protein)-binding protein]. Bhlhe40 interacted with P/CAF and this interaction disrupted the interaction between P/CAF and MyoD. These results suggest that Bhlhe40 functions as a repressor of MyoD by binding to adjacent E-boxes and sequestering P/ CAF from MyoD.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
JournalBiochemical Journal
Issue number2
StatePublished - 1 Sep 2009


  • Basic helix-loop-helix family
  • Member e40 (Bhlhe40)
  • Muscle
  • Myogenic differentiation factor D (MyoD)
  • p300/CBP-associated factor (P/CAF)
  • Peroxisome-proliferator-activated receptor γ co-activator 1α (PGC-1α)


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