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Gene Review

Gata4  -  GATA binding protein 4

Mus musculus

Synonyms: GATA-binding factor 4, Gata-4, Transcription factor GATA-4
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Disease relevance of Gata4


High impact information on Gata4

  • Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription [6].
  • Gata4 is a zinc-finger transcription factor with a role in early cardiac development [6].
  • Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis [7].
  • Late deletion of Gata4 by Cre recombinase driven by the alpha myosin heavy chain promoter did not selectively affect RV development or generation of endocardial cushion mesenchyme but did result in marked myocardial thinning with decreased cardiomyocyte proliferation, as well as double-outlet RV [8].
  • In order to circumvent the early embryonic lethality of Gata4-null embryos and to investigate the role of myocardial Gata4 expression in cardiac development, we used Cre/loxP technology to conditionally delete Gata4 in the myocardium of mice at an early and a late time point in cardiac morphogenesis [8].

Biological context of Gata4

  • Similarities in the phenotypes of Gata4(-/-) chimeras and mice with other genetically engineered mutations that affect gut development suggest that GATA-4 may be involved in the gastric epithelial response to members of the TGF-beta superfamily [9].
  • Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal [8].
  • To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis in the adult small intestine in vivo, we established an inducible, intestine-specific model that results in the synthesis of a transcriptionally inactive Gata4 mutant [10].
  • Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development [11].
  • Furthermore, ectopic p204 triggered the expression of Gata4 and Nkx2.5 in P19 cells. p204 contains a nuclear export signal and was partially translocated to the cytoplasm during the differentiation. p204 from which the nuclear export signal was deleted was not translocated, and it did not induce differentiation [1].

Anatomical context of Gata4


Associations of Gata4 with chemical compounds


Physical interactions of Gata4


Regulatory relationships of Gata4


Other interactions of Gata4

  • We demonstrate that Gata4 and Gata6 have overlapping expression patterns in the early pancreatic epithelium [23].
  • Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype [23].
  • In addition, we show Gata6, but not Gata4, physically interacts with Nkx2.2, an essential islet transcription factor [23].
  • Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos [11].
  • This loop arose in consequence of it that p204 overcame the inhibition of the synergistic activity of Gata4 and Nkx2.5 by the Id proteins [24].

Analytical, diagnostic and therapeutic context of Gata4

  • Mechanistically, cardiac-specific deletion of Gata4 increased cardiomyocyte TUNEL at baseline in embryos and adults as they aged, as well as dramatically increased TUNEL following pressure overload stimulation [2].
  • We correlate their expression with that of muscle markers and the transcription factor GATA-4, using the reverse transcription-polymerase chain reaction (RT-PCR) [25].


  1. p204 is required for the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes: its expression is activated by the cardiac Gata4, Nkx2.5, and Tbx5 proteins. Ding, B., Liu, C.J., Huang, Y., Hickey, R.P., Yu, J., Kong, W., Lengyel, P. J. Biol. Chem. (2006) [Pubmed]
  2. Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Oka, T., Maillet, M., Watt, A.J., Schwartz, R.J., Aronow, B.J., Duncan, S.A., Molkentin, J.D. Circ. Res. (2006) [Pubmed]
  3. Adrenocortical tumorigenesis in transgenic mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen transgene: relationship between ectopic expression of luteinizing hormone receptor and transcription factor GATA-4. Rahman, N.A., Kiiveri, S., Rivero-Müller, A., Levallet, J., Vierre, S., Kero, J., Wilson, D.B., Heikinheimo, M., Huhtaniemi, I. Mol. Endocrinol. (2004) [Pubmed]
  4. Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo). Peterson, R.A., Kiupel, M., Bielinska, M., Kiiveri, S., Heikinheimo, M., Capen, C.C., Wilson, D.B. Vet. Pathol. (2004) [Pubmed]
  5. p300 Functions as a coactivator of transcription factor GATA-4. Dai, Y.S., Markham, B.E. J. Biol. Chem. (2001) [Pubmed]
  6. A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. Svensson, E.C., Huggins, G.S., Lin, H., Clendenin, C., Jiang, F., Tufts, R., Dardik, F.B., Leiden, J.M. Nat. Genet. (2000) [Pubmed]
  7. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Molkentin, J.D., Lin, Q., Duncan, S.A., Olson, E.N. Genes Dev. (1997) [Pubmed]
  8. Morphogenesis of the right ventricle requires myocardial expression of Gata4. Zeisberg, E.M., Ma, Q., Juraszek, A.L., Moses, K., Schwartz, R.J., Izumo, S., Pu, W.T. J. Clin. Invest. (2005) [Pubmed]
  9. Genetic mosaic analysis reveals that GATA-4 is required for proper differentiation of mouse gastric epithelium. Jacobsen, C.M., Narita, N., Bielinska, M., Syder, A.J., Gordon, J.I., Wilson, D.B. Dev. Biol. (2002) [Pubmed]
  10. Gata4 is essential for the maintenance of jejunal-ileal identities in the adult mouse small intestine. Bosse, T., Piaseckyj, C.M., Burghard, E., Fialkovich, J.J., Rajagopal, S., Pu, W.T., Krasinski, S.D. Mol. Cell. Biol. (2006) [Pubmed]
  11. Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element. Rojas, A., De Val, S., Heidt, A.B., Xu, S.M., Bristow, J., Black, B.L. Development (2005) [Pubmed]
  12. Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2. Tevosian, S.G., Albrecht, K.H., Crispino, J.D., Fujiwara, Y., Eicher, E.M., Orkin, S.H. Development (2002) [Pubmed]
  13. SOX7 and GATA-4 are competitive activators of Fgf-3 transcription. Murakami, A., Shen, H., Ishida, S., Dickson, C. J. Biol. Chem. (2004) [Pubmed]
  14. Induction of yolk sac endoderm in GATA-4-deficient embryoid bodies by retinoic acid. Bielinska, M., Wilson, D.B. Mech. Dev. (1997) [Pubmed]
  15. Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity. Aries, A., Paradis, P., Lefebvre, C., Schwartz, R.J., Nemer, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  16. Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells. Ventura, C., Maioli, M. Circ. Res. (2000) [Pubmed]
  17. Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4. Xiang, F., Sakata, Y., Cui, L., Youngblood, J.M., Nakagami, H., Liao, J.K., Liao, R., Chin, M.T. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  18. Intracellular calcium plays an essential role in cardiac development. Porter, G.A., Makuck, R.F., Rivkees, S.A. Dev. Dyn. (2003) [Pubmed]
  19. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Dodou, E., Verzi, M.P., Anderson, J.P., Xu, S.M., Black, B.L. Development (2004) [Pubmed]
  20. Sox7 plays crucial roles in parietal endoderm differentiation in F9 embryonal carcinoma cells through regulating Gata-4 and Gata-6 expression. Futaki, S., Hayashi, Y., Emoto, T., Weber, C.N., Sekiguchi, K. Mol. Cell. Biol. (2004) [Pubmed]
  21. Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter. Viger, R.S., Mertineit, C., Trasler, J.M., Nemer, M. Development (1998) [Pubmed]
  22. Regulation of J6 gene expression by transcription factor GATA-4. Bielinska, M., Wilson, D.B. Biochem. J. (1995) [Pubmed]
  23. Gata6 is an important regulator of mouse pancreas development. Decker, K., Goldman, D.C., L Grasch, C., Sussel, L. Dev. Biol. (2006) [Pubmed]
  24. p204 protein overcomes the inhibition of the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes by Id proteins. Ding, B., Liu, C.J., Huang, Y., Yu, J., Kong, W., Lengyel, P. J. Biol. Chem. (2006) [Pubmed]
  25. Expression of the alpha 6A integrin splice variant in developing mouse embryonic stem cell aggregates and correlation with cardiac muscle differentiation. Thorsteinsdóttir, S., Roelen, B.A., Goumans, M.J., Ward-van Oostwaard, D., Gaspar, A.C., Mummery, C.L. Differentiation (1999) [Pubmed]
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