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

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Title:	P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation
Authors:	Hsiao,SP;Huang,KM;Chang,HY;Chen,SL
Contributors:	生命科學研究所
Keywords:	HELIX-LOOP-HELIX;COACTIVATOR 1-ALPHA PGC-1-ALPHA;BOX TRANSCRIPTION FACTORS;CELL DIFFERENTIATION;SKELETAL-MUSCLE;RECEPTOR-ALPHA;DEC1 STRA13;EXPRESSION;PGC-1;ACTIVATION
Date:	2009
Issue Date:	2010-06-29 19:28:58 (UTC+8)
Publisher:	中央大學
Abstract:	Previously, we found that MRFs (myogenic regulatory factors) regulated the expression of PGC-1 alpha (peroxisome-proliferator-activated receptor gamma co-activator 1 alpha) 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, Bhlhb2, 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 El-box and formed a complex with the basic helix-loop-helix transcription factor MyoD (myogenic differentiation factor D) on the PGC-1 alpha core promoter. We demonstrate that Bhlhe40 binds to the promoters of PGC-1 alpha 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.
Relation:	BIOCHEMICAL JOURNAL
Appears in Collections:	[Graduate Institute of Life Science] journal & Dissertation

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