beta-Catenin/TCF/LEF1 can directly regulate phenylephrine-induced cell hypertrophy and Anf transcription in cardiomyocytes.
beta-Catenin/TCF/LEF1 signaling is implicated in cardiac hypertrophy. We demonstrate that knockdown of beta-catenin attenuates phenylephrine (PE)-induced cardiomyocyte hypertrophy and the up-regulation of the fetal gene Anf. We explore the mechanism through which beta-catenin regulates Anf expression and find a consensus binding sequence on the Anf promoter for TCF/LEF1 family members. LEF1 binds directly to the Anf promoter via this sequence, which shows functional significance, and PE stimulation enhances recruitment of beta-catenin onto the Anf promoter. Thus, we document a direct positive role of beta-catenin on PE-induced cardiomyocyte hypertrophy and identify a new target gene for beta-catenin/TCF/LEF1.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Hai Dian District, Beijing 100191, China.
Chen-Guang
CG
Zhang
Zhu-Qing
ZQ
Jia
Bin-Hong
BH
Li
Hui
H
Zhang
Yi-Nan
YN
Liu
Ping
P
Chen
Kang-Tao
KT
Ma
Chun-Yan
CY
Zhou
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C497575:Lef1 protein, rat; D051821:Lymphoid Enhancer-Binding Factor 1; D051820:TCF Transcription Factors; D051176:beta Catenin; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor