gata5 transcription factor


Summary: A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and is involved in the CELL DIFFERENTIATION of CARDIAC MYOCYTES. In the developing heart, GATA5 becomes restricted to the ENDOCARDIUM and regulates transcription of genes such as cardiac TROPONIN C.

Top Publications

  1. Wakana K, Akiyama Y, Aso T, Yuasa Y. Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis. Cancer Lett. 2006;241:281-8 pubmed
    ..These data suggest that GATA-4/-5 may be involved in ovarian carcinogenesis. ..
  2. Capo Chichi C, Rula M, Smedberg J, Vanderveer L, Parmacek M, Morrisey E, et al. Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells. Dev Biol. 2005;286:574-86 pubmed
    ..This study indicates that the lineage differentiation of ES cells can be manipulated by the expression of GATA factors. ..
  3. Trinh L, Yelon D, Stainier D. Hand2 regulates epithelial formation during myocardial diferentiation. Curr Biol. 2005;15:441-6 pubmed
    ..Furthermore, these results demonstrate that two independent processes, the polarizaton of myocardial precursors and the allocation of proper cell number, contribute to myocardial development. ..
  4. Li N, Wei C, Olena A, Patton J. Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development. Development. 2011;138:1817-26 pubmed publisher
  5. Heicklen Klein A, McReynolds L, Evans T. Using the zebrafish model to study GATA transcription factors. Semin Cell Dev Biol. 2005;16:95-106 pubmed
  6. Guo M, Akiyama Y, House M, Hooker C, Heath E, Gabrielson E, et al. Hypermethylation of the GATA genes in lung cancer. Clin Cancer Res. 2004;10:7917-24 pubmed
    ..001). These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly. ..
  7. Molkentin J. The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem. 2000;275:38949-52 pubmed
  8. Morrisey E, Ip H, Tang Z, Parmacek M. GATA-4 activates transcription via two novel domains that are conserved within the GATA-4/5/6 subfamily. J Biol Chem. 1997;272:8515-24 pubmed
    ..As such these data provide novel insights into the molecular mechanisms that control development of the heart. ..
  9. Fu B, Guo M, Wang S, Campagna D, Luo M, Herman J, et al. Evaluation of GATA-4 and GATA-5 methylation profiles in human pancreatic cancers indicate promoter methylation patterns distinct from other human tumor types. Cancer Biol Ther. 2007;6:1546-52 pubmed
    ..While hypermethylation of GATA-5 seems to be a universal feature among human tumors, infrequent methylation of GATA-4, and its corresponding overexpression, appears unique to pancreatic cancer from other tumor types reported thus far. ..

More Information


  1. Afouda B, Ciau Uitz A, Patient R. GATA4, 5 and 6 mediate TGFbeta maintenance of endodermal gene expression in Xenopus embryos. Development. 2005;132:763-74 pubmed
    ..In addition, examination of gene expression and morphology in later embryos, revealed GATA5 and 6 as the most critical for the development of the gut and the liver. ..
  2. Peterkin T, Gibson A, Loose M, Patient R. The roles of GATA-4, -5 and -6 in vertebrate heart development. Semin Cell Dev Biol. 2005;16:83-94 pubmed
    ..Of the three cardiac GATAs, GATA-4 is by far the most extensively studied, however, loss-of-function data question its presumed dominance during heart development as opposed to hypertrophy. ..
  3. Nemer G, Nemer M. Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells. Development. 2002;129:4045-55 pubmed
    ..This, in turn, suggests that the GATA5 pathway may be relevant to early stages of valvuloseptal development, defects of which account for the majority of human birth malformations. ..
  4. 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. ..
  5. Molkentin J, Lin Q, Duncan S, Olson E. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 1997;11:1061-72 pubmed
    ..We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP. ..
  6. Padang R, Bagnall R, Richmond D, Bannon P, Semsarian C. Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease. J Mol Cell Cardiol. 2012;53:277-81 pubmed publisher
    ..Rare non-synonymous variations in the functionally important GATA5 transcriptional activation domains may be important in the pathogenesis of BAV disease in humans. ..
  7. Rodaway A, Takeda H, Koshida S, Broadbent J, Price B, Smith J, et al. Induction of the mesendoderm in the zebrafish germ ring by yolk cell-derived TGF-beta family signals and discrimination of mesoderm and endoderm by FGF. Development. 1999;126:3067-78 pubmed
  8. Reiter J, Alexander J, Rodaway A, Yelon D, Patient R, Holder N, et al. Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 1999;13:2983-95 pubmed
    ..Together, these results implicate zebrafish Gata5 in controlling the growth, morphogenesis, and differentiation of the heart and endoderm and indicate that Gata5 regulates the expression of the early myocardial gene nkx2.5. ..
  9. 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
  10. Nemer G, Qureshi S, Malo D, Nemer M. Functional analysis and chromosomal mapping of Gata5, a gene encoding a zinc finger DNA-binding protein. Mamm Genome. 1999;10:993-9 pubmed
    ..Thus, Gata5 probably plays a specialized evolutionary conserved role in cardiac development. ..
  11. Jiang Y, Evans T. The Xenopus GATA-4/5/6 genes are associated with cardiac specification and can regulate cardiac-specific transcription during embryogenesis. Dev Biol. 1996;174:258-70 pubmed
    ..The data are consistent with a primary role for the GATA-4/5/6 genes in regulating heart development. ..
  12. Molkentin J, Tymitz K, Richardson J, Olson E. Abnormalities of the genitourinary tract in female mice lacking GATA5. Mol Cell Biol. 2000;20:5256-60 pubmed
    ..These results reveal a specific role of GATA5 in development of the female genitourinary system and suggest that other GATA factors may have functions overlapping those of GATA5 in other tissues. ..
  13. Laforest B, Andelfinger G, Nemer M. Loss of Gata5 in mice leads to bicuspid aortic valve. J Clin Invest. 2011;121:2876-87 pubmed publisher
    ..Mice with mutated Gata5 alleles represent unique models to dissect the mechanisms underlying degenerative aortic valve disease and to develop much-needed preventive and therapeutic interventions. ..
  14. Akiyama Y, Watkins N, Suzuki H, Jair K, van Engeland M, Esteller M, et al. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol. 2003;23:8429-39 pubmed
    ..Selection for silencing of both upstream transcription factors and their target genes in GI cancers could indicate that epigenetic silencing of the involved genes provides a summated contribution to tumor progression. ..
  15. Guo M, House M, Akiyama Y, Qi Y, Capagna D, Harmon J, et al. Hypermethylation of the GATA gene family in esophageal cancer. Int J Cancer. 2006;119:2078-83 pubmed
    ..Our studies demonstrate frequent silencing of GATA-4 and GATA-5, but not GATA-6, in human esophageal neoplasia associated with gene promoter hypermethylation. ..
  16. Reiter J, Kikuchi Y, Stainier D. Multiple roles for Gata5 in zebrafish endoderm formation. Development. 2001;128:125-35 pubmed
    ..Together, these data demonstrate that Gata5 plays multiple roles in endoderm development in zebrafish, and position Gata5 relative to other regulators of endoderm formation. ..
  17. Wen X, Akiyama Y, Pan K, Liu Z, Lu Z, Zhou J, et al. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World J Gastroenterol. 2010;16:1201-8 pubmed
    ..023 and 0.027, two-sides). Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection. ..
  18. Kobayashi D, Jindo T, Naruse K, Takeda H. Development of the endoderm and gut in medaka, Oryzias latipes. Dev Growth Differ. 2006;48:283-95 pubmed
    ..Our results therefore describe both molecular and morphological aspects of medaka digestive system development that will be necessary for the characterization of medaka mutants. ..
  19. Peterkin T, Gibson A, Patient R. Common genetic control of haemangioblast and cardiac development in zebrafish. Development. 2009;136:1465-74 pubmed publisher
  20. Henn D, Perttunen H, Gauer S, Schmied W, Porras C, Such M, et al. GATA5 and endothelial nitric oxide synthase expression in the ascending aorta is related to aortic size and valve morphology. Ann Thorac Surg. 2014;97:2019-25 pubmed publisher
    ..The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different. ..
  21. Thomas P, Sridurongrit S, Ruiz Lozano P, Kaartinen V. Deficient signaling via Alk2 (Acvr1) leads to bicuspid aortic valve development. PLoS ONE. 2012;7:e35539 pubmed publisher
    ..We conclude that signaling via Alk2 is required for appropriate aortic valve development in utero, and that defects in this process lead to indirect secondary complications later in life. ..
  22. Wei D, Bao H, Zhou N, Zheng G, Liu X, Yang Y. GATA5 loss-of-function mutation responsible for the congenital ventriculoseptal defect. Pediatr Cardiol. 2013;34:504-11 pubmed publisher
    ..To the best of the authors' knowledge, this is the first report on the link of functionally compromised GATA5 to human VSD, suggesting potential implications for the early prophylaxis and personalized treatment of VSD. ..
  23. Ren C, Akiyama Y, Miyake S, Yuasa Y. Transcription factor GATA-5 selectively up-regulates mucin gene expression. J Cancer Res Clin Oncol. 2004;130:245-52 pubmed
    ..GATA-5 lacking the zinc finger domain impaired these functions. These findings indicate that GATA-5 may play important roles in the regulation of mucin expression and gastrointestinal epithelial cell differentiation. ..
  24. Tseng W, Jang T, Huang C, Yuh C. An evolutionarily conserved kernel of gata5, gata6, otx2 and prdm1a operates in the formation of endoderm in zebrafish. Dev Biol. 2011;357:541-57 pubmed publisher
    ..This is the first direct evidence for evolutionarily conserved endoderm specification across echinoderms and vertebrates. ..
  25. Benchabane H, Wrana J. GATA- and Smad1-dependent enhancers in the Smad7 gene differentially interpret bone morphogenetic protein concentrations. Mol Cell Biol. 2003;23:6646-61 pubmed
    ..These data thus define how cooperative and noncooperative Smad-dependent transcriptional regulation can function to interpret different BMP concentrations. ..
  26. Kiela P, LeSueur J, Collins J, Ghishan F. Transcriptional regulation of the rat NHE3 gene. Functional interactions between GATA-5 and Sp family transcription factors. J Biol Chem. 2003;278:5659-68 pubmed
    ..This interaction represents a novel regulatory mechanism, which is likely to participate in a gradient of intestinal gene expression along the crypt-villus axis. ..
  27. Jiang J, Li R, Wang J, Liu X, Xu Y, Fang W, et al. Prevalence and spectrum of GATA5 mutations associated with congenital heart disease. Int J Cardiol. 2013;165:570-3 pubmed publisher
  28. Chen B, Yates E, Huang Y, Kogut P, Ma L, Turner J, et al. Alternative promoter and GATA5 transcripts in mouse. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1214-22 pubmed publisher
    ..These findings extend current understanding of the tissue distribution of GATA5 expression and suggests that GATA5 expression and function are more complex than previously appreciated. ..
  29. Chen B, Hsu R, Li Z, Kogut P, Du Q, Rouser K, et al. Upstream stimulatory factor 1 activates GATA5 expression through an E-box motif. Biochem J. 2012;446:89-98 pubmed publisher
  30. Fang R, Olds L, Sibley E. Spatio-temporal patterns of intestine-specific transcription factor expression during postnatal mouse gut development. Gene Expr Patterns. 2006;6:426-32 pubmed
    ..Defining the spatio-temporal expression patterns for intestine-specific transcription factor genes contributes to investigation of the roles that factor gradients play in mediating gut development and differentiation. ..
  31. Jia H, King I, Chopra S, Wan H, Ni T, Jiang C, et al. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proc Natl Acad Sci U S A. 2007;104:14008-13 pubmed
    ..Hence, our studies suggest that Grl regulates embryonic heart growth via opposing Gata5, at least in part through their protein interactions in modulating gene expression. ..
  32. Huggins G, Wong J, Hankinson S, De Vivo I. GATA5 activation of the progesterone receptor gene promoter in breast cancer cells is influenced by the +331G/A polymorphism. Cancer Res. 2006;66:1384-90 pubmed
    ..Our findings suggest that GATA5 interacts with the +331G/A polymorphism to stimulate hPR-B expression in mammary cells, which may contribute to breast cancer susceptibility. ..
  33. Morrisey E, Ip H, Tang Z, Lu M, Parmacek M. GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. Dev Biol. 1997;183:21-36 pubmed
    ..Moreover, these data suggest that GATA-5 may play an important role in the transcriptional program(s) that underlies smooth muscle cell diversity. ..
  34. Gao X, Sedgwick T, Shi Y, Evans T. Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation. Mol Cell Biol. 1998;18:2901-11 pubmed
    ..Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP. ..
  35. Schlange T, Andree B, Arnold H, Brand T. BMP2 is required for early heart development during a distinct time period. Mech Dev. 2000;91:259-70 pubmed
  36. Wei L, Roberts W, Wang L, Yamada M, Zhang S, Zhao Z, et al. Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development. 2001;128:2953-62 pubmed
    ..Thus, our study reveals new biological functions for Rho kinases in regulating major morphogenetic events during early chick and mouse development. ..
  37. Aoki T, David N, Minchiotti G, Saint Etienne L, Dickmeis T, Persico G, et al. Molecular integration of casanova in the Nodal signalling pathway controlling endoderm formation. Development. 2002;129:275-86 pubmed
    ..In addition, casanova efficiently restores later endodermal differentiation in these mutants, but this process requires, in addition, a partial activation of Nodal signalling. ..
  38. Divine J, Staloch L, Haveri H, Jacobsen C, Wilson D, Heikinheimo M, et al. GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene in concert with HNF-1alpha. Am J Physiol Gastrointest Liver Physiol. 2004;287:G1086-99 pubmed
    ..These results demonstrate GATA-4 is critical for intestinal gene expression in vivo and suggest a specific GATA-4/HNF-1alpha physical and functional interaction in Fabpl activation. ..
  39. van Wering H, Huibregtse I, van der Zwan S, de Bie M, Dowling L, Boudreau F, et al. Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter. J Biol Chem. 2002;277:27659-67 pubmed
    ..Parallel mechanisms in other tissues as well as in Drosophila suggest that zinc finger/homeodomain interactions are an efficient pathway of cooperative activation of gene transcription that has been conserved throughout evolution. ..
  40. Wu G, Wang W, Lin Y, Liu S, Chen R. Oxidative stress-induced apoptotic insults to rat osteoblasts are attenuated by nitric oxide pretreatment via GATA-5-involved regulation of Bcl-X L gene expression and protein translocation. Arch Toxicol. 2016;90:905-16 pubmed publisher
    ..The protective mechanisms are mediated by GATA-5-mediated transcriptional induction of Bcl-X L gene, and translocational modulation of Bcl-XL and Bax proteins. ..
  41. Krasinski S, Van Wering H, Tannemaat M, Grand R. Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha. Am J Physiol Gastrointest Liver Physiol. 2001;281:G69-84 pubmed
    ..Synergistic activation is a mechanism by which higher levels of tissue-specific expression might be attained by overlapping expression of specific transcription factors...
  42. Wang H, Liu Z, Li J, Zhao X, Wang Z, Xu H. ?Np63? mediates proliferation and apoptosis in human gastric cancer cells by the regulation of GATA-6. Neoplasma. 2012;59:416-23 pubmed publisher
    ..This is the first study exploring the biological functions and the underlying mechanism of ?Np63? during gastric cancer development. It also identifies potential targets for anti-tumor treatment. ..
  43. 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. ..
  44. Dusing M, Wiginton D. Epithelial lineages of the small intestine have unique patterns of GATA expression. J Mol Histol. 2005;36:15-24 pubmed
    ..The observed distribution suggests that the GATA factors may have distinct roles in lineage allocation, lineage maintenance, and/or terminal differentiation events in small intestine. ..
  45. Afouda B, Hoppler S. Different requirements for GATA factors in cardiogenesis are mediated by non-canonical Wnt signaling. Dev Dyn. 2011;240:649-62 pubmed publisher
    ..We conclude that Wnt11b mediates the differential requirements for GATA factors during vertebrate cardiogenesis. ..
  46. Jonckheere N, Velghe A, Ducourouble M, Copin M, Renes I, Van Seuningen I. The mouse Muc5b mucin gene is transcriptionally regulated by thyroid transcription factor-1 (TTF-1) and GATA-6 transcription factors. FEBS J. 2011;278:282-94 pubmed publisher
    ..The characterization of the structural and functional features of the Muc5b mucin gene will provide us with a strong base to develop studies in murine models aimed at the identification of its biological role in lung pathophysiology. ..
  47. Zerilli F, Bonanno C, Shehi E, Amicarelli G, Adlerstein D, Makrigiorgos G. Methylation-specific loop-mediated isothermal amplification for detecting hypermethylated DNA in simplex and multiplex formats. Clin Chem. 2010;56:1287-96 pubmed publisher
    ..MS-LAMP provides a highly specific isothermal method for methylation detection and is well suited for multiplex approaches. ..
  48. Balakrishnan A, Stearns A, Rhoads D, Ashley S, Tavakkolizadeh A. Defining the transcriptional regulation of the intestinal sodium-glucose cotransporter using RNA-interference mediated gene silencing. Surgery. 2008;144:168-73 pubmed publisher
    ..We, therefore, propose a multifactorial model for SGLT1 regulation, with interactions between HNF1, GATA-5, and CDX2 modulating intestinal glucose absorption. ..
  49. Wang X, Kang G, Campan M, Weisenberger D, Long T, Cozen W, et al. Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors. PLoS ONE. 2011;6:e25985 pubmed publisher
    ..Two new epigenetic subgroups of gastroesophageal adenocarcinomas were identified that differ to some extent in their survival rates, risk factors of exposure, and GATA5 DNA methylation. ..
  50. Peters I, Eggers H, Atschekzei F, Hennenlotter J, Waalkes S, Tränkenschuh W, et al. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int. 2012;110:E144-52 pubmed publisher
  51. Kikuchi Y, Verkade H, Reiter J, Kim C, Chitnis A, Kuroiwa A, et al. Notch signaling can regulate endoderm formation in zebrafish. Dev Dyn. 2004;229:756-62 pubmed
    ..Altogether, these results suggest that Notch signaling plays a role in the formation of the endoderm, possibly in its segregation from the mesoderm. ..
  52. Novikov N, Evans T. Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling. Development. 2013;140:3787-98 pubmed publisher
    ..Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis. ..
  53. Brewer A, Sparks E, Shah A. Transcriptional regulation of the NADPH oxidase isoform, Nox1, in colon epithelial cells: role of GATA-binding factor(s). Free Radic Biol Med. 2006;40:260-74 pubmed
    ..We also identified more distal, upstream regions which act to repress significantly expression from the Nox1 promoter. ..