Transcription factor GATA-4

Definition:

Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development and function. In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it down-regulates endocardial and endothelial gene expression. Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). Acts as a transcriptional activator of ANF in cooperation with NKX2-5 (By similarity). Promotes cardiac myocyte enlargement. Required during testicular development. May play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate degrading enzyme, sphingosine-1-phosphate lyase.

References:

[1]. Yi-Qing Yang, et al. GATA4 loss-of-function mutations underlie familial tetralogy of fallot. Hum Mutat. 2013 Dec;34(12):1662-71. [Content Brief]

[2]. Barbara Gonzalez-Teran, et al. Transcription factor protein interactomes reveal genetic determinants in heart disease. Cell. 2022 Mar 3;185(5):794-814.e30. [Content Brief]

[3]. Yen-Sin Ang, et al. Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human Cardiogenesis. Cell. 2016 Dec 15;167(7):1734-1749.e22. [Content Brief]

[4]. Diana Lourenço, et al. Loss-of-function mutation in GATA4 causes anomalies of human testicular development. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1597-602. [Content Brief]

[5]. Babak Oskouian, et al. Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors. J Biol Chem. 2005 May 6;280(18):18403-10. [Content Brief]

[6]. Yoichi Sunagawa, et al. Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes. J Biol Chem. 2010 Mar 26;285(13):9556-9568. [Content Brief]

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