gata4 transcription factor


Summary: A GATA transcription factor that is expressed in the MYOCARDIUM of developing heart and has been implicated in the differentiation of CARDIAC MYOCYTES. GATA4 is activated by PHOSPHORYLATION and regulates transcription of cardiac-specific genes.

Top Publications

  1. Bouchard M, Taniguchi H, Viger R. The effect of human GATA4 gene mutations on the activity of target gonadal promoters. J Mol Endocrinol. 2009;42:149-60 pubmed publisher
    ..Thus, unlike the heart, where the GATA4 mutations have deleterious effects, our data suggest that they would have a lesser impact on gonadal gene transcription and function. ..
  2. Barske L, Capel B. Estrogen represses SOX9 during sex determination in the red-eared slider turtle Trachemys scripta. Dev Biol. 2010;341:305-14 pubmed publisher
  3. Chen M, Pang Y, Guo Y, Pan J, Liu B, Shen J, et al. GATA4 mutations in Chinese patients with congenital cardiac septal defects. Pediatr Cardiol. 2010;31:85-9 pubmed publisher
    ..Our finding suggests that the mutations in the transcription factor GATA4 might be related to congenital cardiac septal defects in Han ancestry patients. ..
  4. Ieda M, Fu J, Delgado Olguin P, Vedantham V, Hayashi Y, Bruneau B, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142:375-86 pubmed publisher
    ..Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches. ..
  5. Thurisch B, Liang S, Sarioglu N, Schomburg L, BUNGERT J, Dame C. Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads. J Mol Endocrinol. 2009;43:157-69 pubmed publisher
    ..Histology of the teratomas showed predominantly ectodermal and mesodermal structures. Our data demonstrate that Gata4 is critically involved in the function and integrity of the gonads in vivo...
  6. Riazi A, Takeuchi J, Hornberger L, Zaidi S, Amini F, Coles J, et al. NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes. PLoS ONE. 2009;4:e5698 pubmed publisher
    ..This study suggests that NKX2-5 modulates the beta-catenin and GATA4 transcriptional activities in developing human cardiac myocytes. ..
  7. Maitra M, Schluterman M, Nichols H, Richardson J, Lo C, Srivastava D, et al. Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development. Dev Biol. 2009;326:368-77 pubmed publisher
    ..These findings highlight the unique genetic interactions of Gata4 and Gata6 with Tbx5 for normal cardiac morphogenesis in vivo. ..
  8. Liu X, Wang J, Zheng J, Bai K, Liu Z, Wang X, et al. Involvement of a novel GATA4 mutation in atrial septal defects. Int J Mol Med. 2011;28:17-23 pubmed publisher
    ..The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies. ..
  9. Smagulova F, Manuylov N, Leach L, Tevosian S. GATA4/FOG2 transcriptional complex regulates Lhx9 gene expression in murine heart development. BMC Dev Biol. 2008;8:67 pubmed publisher
    ..In summary, the Lhx9 gene represents the first direct target of the GATA4/FOG2 repressor complex in cardiac development. ..

More Information


  1. Saffirio C, Marino B, Digilio M. GATA4 as candidate gene for pericardial defects. Ann Thorac Surg. 2007;84:2137; author reply 2137 pubmed
  2. Wat M, Beck T, Hernandez Garcia A, Yu Z, Veenma D, Garcia M, et al. Mouse model reveals the role of SOX7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1. Hum Mol Genet. 2012;21:4115-25 pubmed publisher
    ..We conclude that haploinsufficiency of Sox7 or Gata4 is sufficient to produce anterior CDH in mice and that haploinsufficiency of SOX7 and GATA4 may each contribute to the development of CDH in individuals with 8p23.1 deletions. ..
  3. Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, et al. Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res. 2012;111:1147-56 pubmed publisher
    ..Quantitative RT-PCR also demonstrated that FACS-sorted 3F2A-transduced cells expressed cardiac-specific genes. GMT gene transfer induced cardiomyocyte-like cells in infarcted hearts. ..
  4. Peterkin T, Gibson A, Patient R. Redundancy and evolution of GATA factor requirements in development of the myocardium. Dev Biol. 2007;311:623-35 pubmed
  5. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature. 2011;475:386-9 pubmed publisher
    ..Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine. ..
  6. Holtzinger A, Evans T. Gata5 and Gata6 are functionally redundant in zebrafish for specification of cardiomyocytes. Dev Biol. 2007;312:613-22 pubmed
    ..In contrast, embryos depleted of Gata4 and Gata6, or Gata4 and Gata5, develop defective heart tubes. Our study identifies a specific pair of vertebrate transcription factor paralogs that is essential for cardiomyocyte specification. ..
  7. Singh M, Li Y, Li S, Cobb R, Zhou D, Lu M, et al. Gata4 and Gata5 cooperatively regulate cardiac myocyte proliferation in mice. J Biol Chem. 2010;285:1765-72 pubmed publisher
    ..These results demonstrate functional redundancy between Gata4 and Gata5 during cardiac development and implicate Gata5 as a candidate modifier gene for congenital heart disease. ..
  8. Hu D, Chen F, Liu Y, Sheng Y, Yang R, Kong X, et al. GATA-4 promotes the differentiation of P19 cells into cardiac myocytes. Int J Mol Med. 2010;26:365-72 pubmed
    ..The overexpression of GATA-4 enhances the differentiation of P19 cells into cardiac myocytes, whereas its down-regulation suppresses this trend...
  9. Rojas A, Schachterle W, Xu S, Black B. An endoderm-specific transcriptional enhancer from the mouse Gata4 gene requires GATA and homeodomain protein-binding sites for function in vivo. Dev Dyn. 2009;238:2588-98 pubmed publisher
    ..These studies establish Gata4 as a direct transcriptional target of homeodomain and GATA transcription factors in the endoderm and support a model in which GATA4 functions in the transcriptional network for pancreas formation. ..
  10. Ito H, Yoshida K, Murakami M, Hagiwara K, Sasaki N, Kobayashi M, et al. Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines. Biochim Biophys Acta. 2011;1811:119-28 pubmed publisher
    ..Thus, high SPL transcription of H1155 cells was regulated by Sp1 and GATA-4/Sp1 complex formation, both of which bind to Sp1 sites of the 5'-SPL promoter. ..
  11. Laforest B, Nemer M. GATA5 interacts with GATA4 and GATA6 in outflow tract development. Dev Biol. 2011;358:368-78 pubmed publisher
    ..The data identify GATA5 as a potential genetic modifier of congenital heart disease and provide insight for elucidating the genetic basis of an important class of human birth defects. ..
  12. Liu J, He X, Corbett S, Lowry S, Graham A, Fassler R, et al. Integrins are required for the differentiation of visceral endoderm. J Cell Sci. 2009;122:233-42 pubmed publisher
    ..Collectively, these results suggest that integrins are required for both the stable adhesion and maturation of visceral endoderm, the latter being mediated through the activation of ERK1/2 and p38 MAPK. ..
  13. Trivedi C, Zhu W, Wang Q, Jia C, Kee H, Li L, et al. Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Dev Cell. 2010;19:450-9 pubmed publisher
    ..These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development. ..
  14. Peng T, Wang L, Zhou S, Li X. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica. 2010;138:1231-40 pubmed publisher
    ..This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted. ..
  15. Zhang X, Wang X, Zhu H, Zhu C, Wang Y, Pu W, et al. Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death. J Mol Cell Cardiol. 2010;49:841-50 pubmed publisher
    ..Thus, both miR-144 and miR-451 may represent new therapeutic agents for the treatment of ischemic heart disease. ..
  16. Salazar M, Consoli F, Villegas V, Caicedo V, Maddaloni V, Daniele P, et al. Search of somatic GATA4 and NKX2.5 gene mutations in sporadic septal heart defects. Eur J Med Genet. 2011;54:306-9 pubmed publisher
  17. Holtzinger A, Rosenfeld G, Evans T. Gata4 directs development of cardiac-inducing endoderm from ES cells. Dev Biol. 2010;337:63-73 pubmed publisher
    ..The results suggest that Gata4 is capable of specifying endoderm fates that facilitate, with temporal and spatial specificity, the generation of cardiomyocyte progenitors from associated mesoderm. ..
  18. Nakajima K, Inagawa M, Uchida C, Okada K, Tane S, Kojima M, et al. Coordinated regulation of differentiation and proliferation of embryonic cardiomyocytes by a jumonji (Jarid2)-cyclin D1 pathway. Development. 2011;138:1771-82 pubmed publisher
    ..Thus, a Jmj-cyclin D1 pathway coordinately regulates proliferation and differentiation of cardiomyocytes. ..
  19. Chen Y, Mao J, Sun Y, Zhang Q, Cheng H, Yan W, et al. A novel mutation of GATA4 in a familial atrial septal defect. Clin Chim Acta. 2010;411:1741-5 pubmed publisher
    ..Both mutations were not identified among healthy controls. T280M mutation of GATA4 is suggested to be associated with ASD in this Chinese family. ..
  20. Li H, Zuo S, He Z, Yang Y, Pasha Z, Wang Y, et al. Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival. Am J Physiol Heart Circ Physiol. 2010;299:H1772-81 pubmed publisher
    ..We conclude that GATA-4 overexpression in MSCs increased both MSC survival and angiogenic potential in ischemic myocardium and may therefore represent a novel and efficient therapeutic approach for postinfarct remodeling. ..
  21. Agnihotri S, Wolf A, Munoz D, Smith C, Gajadhar A, Restrepo A, et al. A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas. J Exp Med. 2011;208:689-702 pubmed publisher
    ..Identification and validation of GATA4 as a TSG and its downstream targets in GBM may yield promising novel therapeutic strategies. ..
  22. Tomita Mitchell A, Maslen C, Morris C, Garg V, Goldmuntz E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet. 2007;44:779-83 pubmed
    ..These data suggest that non-synonymous GATA4 sequence variants are found in a small percentage of patients with septal defects and are very uncommonly found in patients with conotruncal defects. ..
  23. Pilon N, Raiwet D, Viger R, Silversides D. Novel pre- and post-gastrulation expression of Gata4 within cells of the inner cell mass and migratory neural crest cells. Dev Dyn. 2008;237:1133-43 pubmed publisher
    ..Taken altogether, our studies have revealed new Gata4 expression patterns during mouse embryonic development, which are controlled by its 5-kb proximal 5' flanking sequences. ..
  24. Beuling E, Bosse T, aan de Kerk D, Piaseckyj C, Fujiwara Y, Katz S, et al. GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors. Dev Biol. 2008;322:179-89 pubmed publisher
    ..Our data are the first to indicate FOG function and expression in the mammalian small intestine. ..
  25. Snyder M, Huang X, Zhang J. Stat3 directly controls the expression of Tbx5, Nkx2.5, and GATA4 and is essential for cardiomyocyte differentiation of P19CL6 cells. J Biol Chem. 2010;285:23639-46 pubmed publisher
    ..All together, these results demonstrate that Stat3 is required for the differentiation of cardiomyocytes through direct transcriptional regulation of Tbx5, Nkx2.5, and GATA4. ..
  26. Lourenco D, Brauner R, Rybczynska M, Nihoul Fekete C, McElreavey K, Bashamboo A. Loss-of-function mutation in GATA4 causes anomalies of human testicular development. Proc Natl Acad Sci U S A. 2011;108:1597-602 pubmed publisher
    ..The p.Gly221Arg mutant protein also failed to bind to a known protein partner FOG2 that is essential for gonad formation. Our data demonstrate the key role of GATA4 in human testicular development. ..
  27. Nishida H, Miyagawa S, Vieux Rochas M, Morini M, Ogino Y, Suzuki K, et al. Positive regulation of steroidogenic acute regulatory protein gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis. Endocrinology. 2008;149:2090-7 pubmed publisher
    ..These results suggest that Dlx5 and Dlx6 participate in the control of steroidogenesis during testis development. The findings of this study may open the way to analyze human congenital birth defects. ..
  28. Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011;17:1585-93 pubmed publisher
  29. Zhao Y, McLaughlin D, Robinson E, Harvey A, Hookham M, Shah A, et al. Nox2 NADPH oxidase promotes pathologic cardiac remodeling associated with Doxorubicin chemotherapy. Cancer Res. 2010;70:9287-97 pubmed publisher
  30. Schlesinger J, Schueler M, Grunert M, Fischer J, Zhang Q, Krueger T, et al. The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs. PLoS Genet. 2011;7:e1001313 pubmed publisher
    ..This opens a new perspective to understand heart development and the complexity cardiovascular disorders. ..
  31. Cai K, Capo Chichi C, Rula M, Yang D, Xu X. Dynamic GATA6 expression in primitive endoderm formation and maturation in early mouse embryogenesis. Dev Dyn. 2008;237:2820-9 pubmed publisher
  32. van Berlo J, Elrod J, Aronow B, Pu W, Molkentin J. Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo. Proc Natl Acad Sci U S A. 2011;108:12331-6 pubmed publisher
    ..Moreover, hearts from Gata4-S105A mice had significant changes in the expression of hypertrophy-inducible, fetal, and remodeling-related genes. ..
  33. Agnihotri S, Wolf A, Picard D, Hawkins C, Guha A. GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system. Oncogene. 2009;28:3033-46 pubmed publisher
    ..Collectively, we show that GATA4 is expressed in the embryonic and adult CNS and acts as a negative regulator of astrocyte proliferation and growth. ..
  34. Lin X, Huo Z, Liu X, Zhang Y, Li L, Zhao H, et al. A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet. 2010;55:662-7 pubmed publisher
    ..Biological analysis revealed clearly decreased transcriptional activity of GATA6 Ser184Asn in vitro. All these data suggest that GATA6 Ser184Asn is a novel mutation associated with CHDs and has an important role in disease pathogenesis. ..
  35. Li H, Zuo S, Pasha Z, Yu B, He Z, Wang Y, et al. GATA-4 promotes myocardial transdifferentiation of mesenchymal stromal cells via up-regulating IGFBP-4. Cytotherapy. 2011;13:1057-65 pubmed publisher
    ..Overexpression of GATA-4 significantly increases MSC differentiation into a myocardial phenotype, which might be associated with the up-regulation of IGFBP-4. ..
  36. Kuhl A, Ross S, Gaido K. CCAAT/enhancer binding protein beta, but not steroidogenic factor-1, modulates the phthalate-induced dysregulation of rat fetal testicular steroidogenesis. Endocrinology. 2007;148:5851-64 pubmed
    ..In conclusion, this study presents a snapshot of changes in the structure of transcriptional machinery and proposes a mechanism of action resulting from DBP exposure. ..
  37. Miranda Carboni G, Guemes M, Bailey S, Anaya E, Corselli M, Peault B, et al. GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription. Mol Endocrinol. 2011;25:1126-36 pubmed publisher
    ..As such, knockdown of GATA4 reduced recruitment of ER? to DNA. Our study illustrates that GATA4 is a pioneer factor for ER? recruitment to osteoblast-specific enhancers. ..
  38. Patankar J, Chandak P, Obrowsky S, Pfeifer T, Diwoky C, Uellen A, et al. Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice. Am J Physiol Endocrinol Metab. 2011;300:E478-88 pubmed publisher
    ..In addition, we show that increased GLP-1 release in GATA4iKO mice decreases the risk for development of insulin resistance. ..
  39. Butler T, Esposito G, Blue G, Cole A, Costa M, Waddell L, et al. GATA4 mutations in 357 unrelated patients with congenital heart malformation. Genet Test Mol Biomarkers. 2010;14:797-802 pubmed publisher
    ..Our data expand the spectrum of mutations associated with cardiac septal defects but do not support GATA4 mutations as a common cause of CHD. ..
  40. Mazaud Guittot S, Bouchard M, Robert Grenon J, Robert C, Goodyer C, Silversides D, et al. Conserved usage of alternative 5' untranslated exons of the GATA4 gene. PLoS ONE. 2009;4:e8454 pubmed publisher
  41. Zhao R, Watt A, Battle M, Li J, Bondow B, Duncan S. Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Dev Biol. 2008;317:614-9 pubmed publisher
    ..Our data support a model whereby GATA4 or GATA6 are essential for expression of the network of transcription factors that regulate the onset of cardiac myocyte gene expression during mammalian development. ..
  42. Posch M, Perrot A, Schmitt K, Mittelhaus S, Esenwein E, Stiller B, et al. Mutations in GATA4, NKX2.5, CRELD1, and BMP4 are infrequently found in patients with congenital cardiac septal defects. Am J Med Genet A. 2008;146A:251-3 pubmed
  43. Nel Themaat L, Jang C, Stewart M, Akiyama H, Viger R, Behringer R. Sertoli cell behaviors in developing testis cords and postnatal seminiferous tubules of the mouse. Biol Reprod. 2011;84:342-50 pubmed publisher
    ..This revealed the physical relationship between Sertoli and germ cells in developing testis cords and provided a novel perspective on Sertoli cell development...
  44. De Luca A, Sarkozy A, Ferese R, Consoli F, Lepri F, Dentici M, et al. New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle. Clin Genet. 2011;80:184-90 pubmed publisher
    ..5 to a small number of TOF cases. ..
  45. Lu Y, Shioda N, Yamamoto Y, Han F, Fukunaga K. Transcriptional upregulation of calcineurin Abeta by endothelin-1 is partially mediated by calcium/calmodulin-dependent protein kinase IIdelta3 in rat cardiomyocytes. Biochim Biophys Acta. 2010;1799:429-41 pubmed publisher
  46. Wang J, Lu Y, Chen H, Yin M, Yu T, Fu Q. Investigation of somatic NKX2-5, GATA4 and HAND1 mutations in patients with tetralogy of Fallot. Pathology. 2011;43:322-6 pubmed publisher
    ..Our study shows no evidence of somatic NKX2-5, GATA4 and HAND1 mutations playing a role in the pathogenesis of TOF. Our findings suggest that the GATA4 and HAND1 germline mutations are associated with non-syndromic CHD. ..
  47. Takeuchi J, Bruneau B. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature. 2009;459:708-11 pubmed publisher
    ..The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes. ..
  48. Zhang W, Li X, Ma Z, Zhang J, Zhou S, Li T, et al. GATA4 and NKX2.5 gene analysis in Chinese Uygur patients with congenital heart disease. Chin Med J (Engl). 2009;122:416-9 pubmed
    ..There were no reported NKX2.5 mutations in the patients. Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population. ..
  49. Battle M, Bondow B, Iverson M, Adams S, Jandacek R, Tso P, et al. GATA4 is essential for jejunal function in mice. Gastroenterology. 2008;135:1676-1686.e1 pubmed publisher
    ..Our data demonstrate that GATA4 is essential for jejunal function including fat and cholesterol absorption and confirm that GATA4 plays a pivotal role in determining jejunal vs ileal identity. ..
  50. Kyrönlahti A, Rämö M, Tamminen M, Unkila Kallio L, Butzow R, Leminen A, et al. GATA-4 regulates Bcl-2 expression in ovarian granulosa cell tumors. Endocrinology. 2008;149:5635-42 pubmed publisher
    ..Our results reveal a previously unknown relationship between GATA-4 and Bcl-2 in mammalian granulosa cells and GCTs, and suggest that GATA-4 influences granulosa cell fate by transactivating Bcl-2. ..
  51. Xiong F, Li Q, Zhang C, Chen Y, Li P, Wei X, et al. Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease. Cardiovasc Pathol. 2013;22:141-5 pubmed publisher
    ..They also revealed that the variation of the NKX2.5 gene may not be a risk factor for sporadic patients with congenital heart disease in this population. ..
  52. Benoit Y, Paré F, Francoeur C, Jean D, Tremblay E, Boudreau F, et al. Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line. Am J Physiol Gastrointest Liver Physiol. 2010;298:G504-17 pubmed publisher
    ..These observations show that, in cooperation with Cdx2, HNF-1alpha acts as a key factor on human intestinal cells to trigger the onset of their functional differentiation program whereas GATA-4 appears to promote morphological changes. ..
  53. Protze S, Khattak S, Poulet C, Lindemann D, Tanaka E, Ravens U. A new approach to transcription factor screening for reprogramming of fibroblasts to cardiomyocyte-like cells. J Mol Cell Cardiol. 2012;53:323-32 pubmed publisher
    ..Furthermore, our results point to the importance of verifying multiple lineage specific genes when assessing reprogramming. ..