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Gene Review

GATA4  -  GATA binding protein 4

Homo sapiens

Synonyms: ASD2, GATA-binding factor 4, TACHD, TOF, Transcription factor GATA-4, ...
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Disease relevance of GATA4


High impact information on GATA4


Chemical compound and disease context of GATA4


Biological context of GATA4


Anatomical context of GATA4


Associations of GATA4 with chemical compounds

  • We further revealed that lysine 366 of GATA4 constituted a major sumyolation site [15].
  • A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function [21].
  • Moreover, the bHLH domain of dHAND directly interacted with the CH3 domain of p300 suggesting the existence of a higher order complex between GATA4, dHAND, and p300 [22].
  • Conversion of lysine 366 to arginine 366 resulted in reduced GATA4 nuclear occupation, suggesting that SUMO modification may also modulate GATA4 nuclear localization [15].
  • Furthermore, ascorbic acid induced the expression of cardiac genes, including GATA4, alpha-MHC, and beta-MHC in untransfected ES cells in a developmentally controlled manner [23].

Physical interactions of GATA4

  • In previous studies we have established that GATA-4 binding to the EPHX1 core promoter is critical for EPHX1 expression [24].
  • The LPH promoter contains binding sites that mediate activation by members of the GATA-4, -5, and -6 subfamily, but little is known about their individual contribution to LPH regulation in vivo [25].
  • PGE2 increased GATA-4 binding to the Cyp19 promoter [26].
  • GATA-4 binds to an upstream element of the human alpha2(I) collagen gene (COL1A2) and inhibits transcription in fibroblasts [27].
  • The in silico analysis of the upstream sequence of the oxytocin receptor predicted putative binding sites for Gata4 and Nkx2 [28].

Regulatory relationships of GATA4

  • Coexpression of GATA-4 stimulated EPHX1 promoter activity up to 7.5-fold in a dose-dependent manner [29].
  • Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins [30].
  • Furthermore, forced GATA-4 expression in Caco-2 cells enhances maintenance of claudin-2 expression during differentiation [31].
  • CDX2 and HNF-1alpha were expressed along the entire intestine whereas GATA-4 was undetectable in the colon [31].
  • In KK-1 granulosa tumour cells, which resemble normal granulosa cells and express inhibin-alpha, we found that TGF-beta upregulated GATA-4 expression [32].
  • GATA-4 enhanced Bcl-2 and cyclin D2 promoter activity in murine GCT cells [33].

Other interactions of GATA4


Analytical, diagnostic and therapeutic context of GATA4


  1. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Caslini, C., Capo-chichi, C.D., Roland, I.H., Nicolas, E., Yeung, A.T., Xu, X.X. Oncogene (2006) [Pubmed]
  2. Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines. Bai, Y., Akiyama, Y., Nagasaki, H., Yagi, O.K., Kikuchi, Y., Saito, N., Takeshita, K., Iwai, T., Yuasa, Y. Mol. Carcinog. (2000) [Pubmed]
  3. GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease. Pehlivan, T., Pober, B.R., Brueckner, M., Garrett, S., Slaugh, R., Van Rheeden, R., Wilson, D.B., Watson, M.S., Hing, A.V. Am. J. Med. Genet. (1999) [Pubmed]
  4. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Garg, V., Kathiriya, I.S., Barnes, R., Schluterman, M.K., King, I.N., Butler, C.A., Rothrock, C.R., Eapen, R.S., Hirayama-Yamada, K., Joo, K., Matsuoka, R., Cohen, J.C., Srivastava, D. Nature (2003) [Pubmed]
  5. GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. Hellebrekers, D.M., Lentjes, M.H., van den Bosch, S.M., Melotte, V., Wouters, K.A., Daenen, K.L., Smits, K.M., Akiyama, Y., Yuasa, Y., Sanduleanu, S., Khalid-de Bakker, C.A., Jonkers, D., Weijenberg, M.P., Louwagie, J., van Criekinge, W., Carvalho, B., Meijer, G.A., Baylin, S.B., Herman, J.G., de Bruïne, A.P., van Engeland, M. Clin. Cancer Res. (2009) [Pubmed]
  6. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Molkentin, J.D., Lu, J.R., Antos, C.L., Markham, B., Richardson, J., Robbins, J., Grant, S.R., Olson, E.N. Cell (1998) [Pubmed]
  7. Differentiation of embryonic stem cells is induced by GATA factors. Fujikura, J., Yamato, E., Yonemura, S., Hosoda, K., Masui, S., Nakao, K., Miyazaki Ji, J., Niwa, H. Genes Dev. (2002) [Pubmed]
  8. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Crispino, J.D., Lodish, M.B., Thurberg, B.L., Litovsky, S.H., Collins, T., Molkentin, J.D., Orkin, S.H. Genes Dev. (2001) [Pubmed]
  9. Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA. Charron, F., Tsimiklis, G., Arcand, M., Robitaille, L., Liang, Q., Molkentin, J.D., Meloche, S., Nemer, M. Genes Dev. (2001) [Pubmed]
  10. Hypermethylation of the GATA gene family in esophageal cancer. Guo, M., House, M.G., Akiyama, Y., Qi, Y., Capagna, D., Harmon, J., Baylin, S.B., Brock, M.V., Herman, J.G. Int. J. Cancer (2006) [Pubmed]
  11. Protein Kinase C Regulates Internal Initiation of Translation of the GATA-4 mRNA following Vasopressin-induced Hypertrophy of Cardiac Myocytes. Sharma, A., Masri, J., Jo, O.D., Bernath, A., Martin, J., Funk, A., Gera, J. J. Biol. Chem. (2007) [Pubmed]
  12. A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Xin, M., Davis, C.A., Molkentin, J.D., Lien, C.L., Duncan, S.A., Richardson, J.A., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes. Liang, Q., Wiese, R.J., Bueno, O.F., Dai, Y.S., Markham, B.E., Molkentin, J.D. Mol. Cell. Biol. (2001) [Pubmed]
  14. Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts. Wang, J., Li, A., Wang, Z., Feng, X., Olson, E.N., Schwartz, R.J. Mol. Cell. Biol. (2007) [Pubmed]
  15. SUMO-1 modification activated GATA4-dependent cardiogenic gene activity. Wang, J., Feng, X.H., Schwartz, R.J. J. Biol. Chem. (2004) [Pubmed]
  16. Follicle-stimulating hormone-induced activation of gata4 contributes in the up-regulation of cyp19 expression in rat granulosa cells. Kwintkiewicz, J., Cai, Z., Stocco, C. Mol. Endocrinol. (2007) [Pubmed]
  17. Assignment of the transcription factor GATA4 gene to human chromosome 8 and mouse chromosome 14: Gata4 is a candidate gene for Ds (disorganization). White, R.A., Dowler, L.L., Pasztor, L.M., Gatson, L.L., Adkison, L.R., Angeloni, S.V., Wilson, D.B. Genomics (1995) [Pubmed]
  18. Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of congenital heart defects. Giglio, S., Graw, S.L., Gimelli, G., Pirola, B., Varone, P., Voullaire, L., Lerzo, F., Rossi, E., Dellavecchia, C., Bonaglia, M.C., Digilio, M.C., Giannotti, A., Marino, B., Carrozzo, R., Korenberg, J.R., Danesino, C., Sujansky, E., Dallapiccola, B., Zuffardi, O. Circulation (2000) [Pubmed]
  19. The human Cx40 promoter polymorphism -44G-->A differentially affects transcriptional regulation by Sp1 and GATA4. Firouzi, M., Bierhuizen, M.F., Kok, B., Teunissen, B.E., Jansen, A.T., Jongsma, H.J., Groenewegen, W.A. Biochim. Biophys. Acta (2006) [Pubmed]
  20. Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation. Gao, X., Sedgwick, T., Shi, Y.B., Evans, T. Mol. Cell. Biol. (1998) [Pubmed]
  21. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function. Su, K., Li, X., Edberg, J.C., Wu, J., Ferguson, P., Kimberly, R.P. J. Immunol. (2004) [Pubmed]
  22. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. Dai, Y.S., Cserjesi, P., Markham, B.E., Molkentin, J.D. J. Biol. Chem. (2002) [Pubmed]
  23. Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Takahashi, T., Lord, B., Schulze, P.C., Fryer, R.M., Sarang, S.S., Gullans, S.R., Lee, R.T. Circulation (2003) [Pubmed]
  24. CCAAT/enhancer-binding protein alpha (C/EBPalpha) activates transcription of the human microsomal epoxide hydrolase gene (EPHX1) through the interaction with DNA-bound NF-Y. Zhu, Q.S., Qian, B., Levy, D. J. Biol. Chem. (2004) [Pubmed]
  25. Complex regulation of the lactase-phlorizin hydrolase promoter by GATA-4. van Wering, H.M., Bosse, T., Musters, A., de Jong, E., de Jong, N., Hogen Esch, C.E., Boudreau, F., Swain, G.P., Dowling, L.N., Montgomery, R.K., Grand, R.J., Krasinski, S.D. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  26. Prostaglandin E2 increases cyp19 expression in rat granulosa cells: Implication of GATA-4. Cai, Z., Kwintkiewicz, J., Young, M.E., Stocco, C. Mol. Cell. Endocrinol. (2007) [Pubmed]
  27. GATA-4 binds to an upstream element of the human alpha2(I) collagen gene (COL1A2) and inhibits transcription in fibroblasts. Wang, L., Tanaka, S., Ramirez, F. Matrix Biol. (2005) [Pubmed]
  28. Upregulations of Gata4 and oxytocin receptor are important in cardiomyocyte differentiation processes of P19CL6 cells. Uchida, S., Fuke, S., Tsukahara, T. J. Cell. Biochem. (2007) [Pubmed]
  29. Regulation of human microsomal epoxide hydrolase gene (EPHX1) expression by the transcription factor GATA-4. Zhu, Q.S., Qian, B., Levy, D. Biochim. Biophys. Acta (2004) [Pubmed]
  30. Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins. Yamagata, T., Nishida, J., Sakai, R., Tanaka, T., Honda, H., Hirano, N., Mano, H., Yazaki, Y., Hirai, H. Mol. Cell. Biol. (1995) [Pubmed]
  31. Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. Escaffit, F., Boudreau, F., Beaulieu, J.F. J. Cell. Physiol. (2005) [Pubmed]
  32. GATA-4 is a granulosa cell factor employed in inhibin-alpha activation by the TGF-beta pathway. Anttonen, M., Parviainen, H., Kyrönlahti, A., Bielinska, M., Wilson, D.B., Ritvos, O., Heikinheimo, M. J. Mol. Endocrinol. (2006) [Pubmed]
  33. GATA-4 regulates Bcl-2 expression in ovarian granulosa cell tumors. Kyrönlahti, A., Rämö, M., Tamminen, M., Unkila-Kallio, L., Butzow, R., Leminen, A., Nemer, M., Rahman, N., Huhtaniemi, I., Heikinheimo, M., Anttonen, M. Endocrinology (2008) [Pubmed]
  34. Identification and validation of an ERBB2 gene expression signature in breast cancers. Bertucci, F., Borie, N., Ginestier, C., Groulet, A., Charafe-Jauffret, E., Adélaïde, J., Geneix, J., Bachelart, L., Finetti, P., Koki, A., Hermitte, F., Hassoun, J., Debono, S., Viens, P., Fert, V., Jacquemier, J., Birnbaum, D. Oncogene (2004) [Pubmed]
  35. Biochemical analyses of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies. Kasahara, H., Benson, D.W. Cardiovasc. Res. (2004) [Pubmed]
  36. Identification of p300-targeted acetylated residues in GATA4 during hypertrophic responses in cardiac myocytes. Takaya, T., Kawamura, T., Morimoto, T., Ono, K., Kita, T., Shimatsu, A., Hasegawa, K. J. Biol. Chem. (2008) [Pubmed]
  37. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Hirayama-Yamada, K., Kamisago, M., Akimoto, K., Aotsuka, H., Nakamura, Y., Tomita, H., Furutani, M., Imamura, S., Takao, A., Nakazawa, M., Matsuoka, R. Am. J. Med. Genet. A (2005) [Pubmed]
  38. Regulation of Ncx1 Expression: IDENTIFICATION OF REGULATORY ELEMENTS MEDIATING CARDIAC-SPECIFIC EXPRESSION AND UP-REGULATION. Xu, L., Renaud, L., M??ller, J.G., Baicu, C.F., Bonnema, D.D., Zhou, H., Kappler, C.S., Kubalak, S.W., Zile, M.R., Conway, S.J., Menick, D.R. J. Biol. Chem. (2006) [Pubmed]
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