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Gene Review

Gata6  -  GATA binding protein 6

Mus musculus

Synonyms: AA410133, GATA-6, GATA-binding factor 6, Transcription factor GATA-6
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Disease relevance of Gata6

  • The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1) [1].
  • Sox7 plays crucial roles in parietal endoderm differentiation in F9 embryonal carcinoma cells through regulating Gata-4 and Gata-6 expression [2].
  • Overexpression of either GATA4 or GATA6 was sufficient to induce cardiomyocyte hypertrophy characterized by enhanced sarcomeric organization, a greater than 2-fold increase in cell surface area, and a significant increase in total protein accumulation [3].
  • In the present work, GATA-6 mRNA was detected in adult mouse lung, purified mouse type II epithelial cells, and differentiated mouse pulmonary adenocarcinoma cells (MLE-15 cells), being co-expressed with TTF-1 mRNA [4].
  • To model the increase in endogenous GATA4 and GATA6 transcriptional activity that occurs in response to hypertrophic stimulation, each factor was overexpressed in cardiomyocytes using recombinant adenovirus [3].

High impact information on Gata6

  • GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo [5].
  • GATA6 belongs to a family of zinc finger transcription factors that play important roles in transducing nuclear events that regulate cellular differentiation and embryonic morphogenesis in vertebrate species [5].
  • In addition, these data demonstrate that GATA6 is required for establishment of the endodermally derived bronchial epithelium [5].
  • Finally, to examine the function of GATA6 during later embryonic development, GATA6(-/-)-C57BL/6 chimeric mice were generated. lacZ-tagged GATA6(-/-) ES cells contributed to all embryonic tissues with the exception of the endodermally derived bronchial epithelium [5].
  • These findings reveal a threshold of GATA4 and GATA6 activity that is required for gene expression in the developing cardiovascular system and underscore the potential of recessive mutations to perturb the delicate regulation of cardiovascular development [6].

Biological context of Gata6


Anatomical context of Gata6

  • We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme [10].
  • It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development [10].
  • A central feature of this altered cellular identity is the switch from predominant expression of Gata6 (endogenous to the adrenal cortex) to Gata4, which defines cellular identity in the ovary [11].
  • Of the two genes, however, only Gata6 was expressed in vascular smooth muscle [8].
  • Cotransfection experiments demonstrate that the human Dab2 promoter can be transactivated by forced expression of GATA-6 in NIH-3T3 cells [12].

Associations of Gata6 with chemical compounds


Physical interactions of Gata6


Regulatory relationships of Gata6

  • Transgenic mice expressing Gata6 cDNA under the control of the human Surfactant Protein-C (SP-C) promoter were generated and their lungs were analyzed during fetal stages [22].
  • Surprisingly, the specificity of GATA-6-induced transactivation of the Dab2 promoter is not mediated through its zinc finger DNA-binding domain [12].
  • Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter [23].
  • Using the P19-CL6 embryonal carcinoma (EC) cell line as an in vitro model of cardiogenesis, we show that GATA6 is the most abundantly expressed of the GATA factors in presumptive cardiac cells [24].
  • This analysis revealed that GATA-6 strongly repressed telokin promoter activity [20].

Other interactions of Gata6

  • Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm [10].
  • In addition, we show Gata6, but not Gata4, physically interacts with Nkx2.2, an essential islet transcription factor [7].
  • RNase protection analysis showed that Gata6 is abundantly expressed in the heart, stomach, intestine, and ovaries of the adult mouse [8].
  • Taken together, these data demonstrate that the mitogen-responsive phosphoprotein Dab2 is a downstream target of GATA-6 in the visceral endoderm [12].
  • Taken together these results indicate that GATA-4 is not essential for terminal differentiation of cardiomyocytes and suggest that additional GATA-binding proteins known to be in cardiac tissue, such as GATA-5 or GATA-6, may compensate for a lack of GATA-4 [25].

Analytical, diagnostic and therapeutic context of Gata6


  1. GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo. Zhang, Y., Rath, N., Hannenhalli, S., Wang, Z., Cappola, T., Kimura, S., Atochina-Vasserman, E., Lu, M.M., Beers, M.F., Morrisey, E.E. Development (2007) [Pubmed]
  2. 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]
  3. The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. Liang, Q., De Windt, L.J., Witt, S.A., Kimball, T.R., Markham, B.E., Molkentin, J.D. J. Biol. Chem. (2001) [Pubmed]
  4. GATA-6 activates transcription of thyroid transcription factor-1. Shaw-White, J.R., Bruno, M.D., Whitsett, J.A. J. Biol. Chem. (1999) [Pubmed]
  5. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Morrisey, E.E., Tang, Z., Sigrist, K., Lu, M.M., Jiang, F., Ip, H.S., Parmacek, M.S. Genes Dev. (1998) [Pubmed]
  6. 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]
  7. Gata6 is an important regulator of mouse pancreas development. Decker, K., Goldman, D.C., L Grasch, C., Sussel, L. Dev. Biol. (2006) [Pubmed]
  8. The gene for transcription factor GATA-6 resides on mouse chromosome 18 and is expressed in myocardium and vascular smooth muscle. Narita, N., Heikinheimo, M., Bielinska, M., White, R.A., Wilson, D.B. Genomics (1996) [Pubmed]
  9. Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells. Hay, D.C., Sutherland, L., Clark, J., Burdon, T. Stem Cells (2004) [Pubmed]
  10. The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development. Keijzer, R., van Tuyl, M., Meijers, C., Post, M., Tibboel, D., Grosveld, F., Koutsourakis, M. Development (2001) [Pubmed]
  11. Origin and identity of adrenocortical tumors in inhibin knockout mice: implications for cellular plasticity in the adrenal cortex. Looyenga, B.D., Hammer, G.D. Mol. Endocrinol. (2006) [Pubmed]
  12. The gene encoding the mitogen-responsive phosphoprotein Dab2 is differentially regulated by GATA-6 and GATA-4 in the visceral endoderm. Morrisey, E.E., Musco, S., Chen, M.Y., Lu, M.M., Leiden, J.M., Parmacek, M.S. J. Biol. Chem. (2000) [Pubmed]
  13. Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells. Capo-Chichi, C.D., Rula, M.E., Smedberg, J.L., Vanderveer, L., Parmacek, M.S., Morrisey, E.E., Godwin, A.K., Xu, X.X. Dev. Biol. (2005) [Pubmed]
  14. GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Morrisey, E.E., Ip, H.S., Lu, M.M., Parmacek, M.S. Dev. Biol. (1996) [Pubmed]
  15. Widespread expression of an extended peptide sequence of GATA-6 during murine embryogenesis and non-equivalence of RNA and protein expression domains. Brewer, A., Nemer, G., Gove, C., Rawlins, F., Nemer, M., Patient, R., Pizzey, J. Mech. Dev. (2002) [Pubmed]
  16. Rapid induction of GATA transcription factors in developing mouse intestine following glucocorticoid administration. Oesterreicher, T.J., Henning, S.J. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  17. GATA-6 is required for maturation of the lung in late gestation. Liu, C., Morrisey, E.E., Whitsett, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  18. Regulation of the A3 adenosine receptor gene in vascular smooth muscle cells: role of a cAMP and GATA element. Yaar, R., Cataldo, L.M., Tzatsos, A., Francis, C.E., Zhao, Z., Ravid, K. Mol. Pharmacol. (2002) [Pubmed]
  19. Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart. Molkentin, J.D., Antos, C., Mercer, B., Taigen, T., Miano, J.M., Olson, E.N. Dev. Biol. (2000) [Pubmed]
  20. GATA-6 can act as a positive or negative regulator of smooth muscle-specific gene expression. Yin, F., Herring, B.P. J. Biol. Chem. (2005) [Pubmed]
  21. Codon 12 region of mouse K-ras gene is the site for in vitro binding of transcription factors GATA-6 and NF-Y. Gorshkova, E.V., Kaledin, V.I., Kobzev, V.F., Merkulova, T.I. Biochemistry Mosc. (2005) [Pubmed]
  22. Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression. Koutsourakis, M., Keijzer, R., Visser, P., Post, M., Tibboel, D., Grosveld, F. Mech. Dev. (2001) [Pubmed]
  23. GATA6 regulates differentiation of distal lung epithelium. Yang, H., Lu, M.M., Zhang, L., Whitsett, J.A., Morrisey, E.E. Development (2002) [Pubmed]
  24. Wnt2 is a direct downstream target of GATA6 during early cardiogenesis. Alexandrovich, A., Arno, M., Patient, R.K., Shah, A.M., Pizzey, J.A., Brewer, A.C. Mech. Dev. (2006) [Pubmed]
  25. Cardiomyocyte differentiation by GATA-4-deficient embryonic stem cells. Narita, N., Bielinska, M., Wilson, D.B. Development (1997) [Pubmed]
  26. Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts. Fischer, A., Klattig, J., Kneitz, B., Diez, H., Maier, M., Holtmann, B., Englert, C., Gessler, M. Mol. Cell. Biol. (2005) [Pubmed]
  27. Transcription factors GATA-4 and GATA-6 in human adrenocortical tumors. Kiiveri, S., Liu, J., Heikkilä, P., Arola, J., Lehtonen, E., Voutilainen, R., Heikinheimo, M. Endocr. Res. (2004) [Pubmed]
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