title: EGF is required for cardiac differentiation of P19CL6 cells through interaction with GATA-4 in a time- and dose-dependent manner.
abstract: The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Ke Xue Da Dao 100, Zhengzhou, 450001, Henan, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Ma
authors.forename: Yang-Liu
authors.initials: YL
authors.lastname: Song
authors.forename: Liyun
authors.initials: L
authors.lastname: Xiao
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Xue
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laforest
authors.forename: Hiba
authors.initials: H
authors.lastname: Komati
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Zhu-Qing
authors.initials: ZQ
authors.lastname: Jia
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zhou
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Mona
authors.initials: M
authors.lastname: Nemer
authors.forename: Shan-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Bai
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D006652:Histological Techniques; D047468:Immunoprecipitation; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D050991:GATA4 Transcription Factor; D004815:Epidermal Growth Factor