gata6 transcription factor


Summary: A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and regulates vascular smooth muscle CELL DIFFERENTIATION.

Top Publications

  1. 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. ..
  2. Fl├╝ck C, Miller W. GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1. Mol Endocrinol. 2004;18:1144-57 pubmed
    ..Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells. ..
  3. Kang M, Piliszek A, Artus J, Hadjantonakis A. FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse. Development. 2013;140:267-79 pubmed publisher
    ..Instead, depending on concentration, we noted no effect or conversion of all ICM cells to GATA6-positive PrE. We propose that heterogeneities in the availability of FGF produce the salt-and-pepper distribution of lineage-biased cells...
  4. Kiiveri S, Liu J, Arola J, Heikkila P, Kuulasmaa T, Lehtonen E, et al. Transcription factors GATA-6, SF-1, and cell proliferation in human adrenocortical tumors. Mol Cell Endocrinol. 2005;233:47-56 pubmed
    ..Taken together, the present and earlier results link GATA-6 to adrenocortical steroidogenesis and to the benign adrenocortical phenotype. ..
  5. Shureiqi I, Zuo X, Broaddus R, Wu Y, Guan B, Morris J, et al. The transcription factor GATA-6 is overexpressed in vivo and contributes to silencing 15-LOX-1 in vitro in human colon cancer. FASEB J. 2007;21:743-53 pubmed
    ..Maintaining 15-LOX-1 transcriptional silencing in cancer cells is a multifactorial process involving GATA-6 overexpression and other regulatory events. ..
  6. Al azzeh E, Fegert P, Blin N, Gott P. Transcription factor GATA-6 activates expression of gastroprotective trefoil genes TFF1 and TFF2. Biochim Biophys Acta. 2000;1490:324-32 pubmed
    ..The functional contribution of GATA binding sequences in the reverse orientation was further characterized by reporter gene assays using TFF2 deletion constructs and by gel shift experiments. ..
  7. Morris S, Teo R, Li H, Robson P, Glover D, Zernicka Goetz M. Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proc Natl Acad Sci U S A. 2010;107:6364-9 pubmed publisher
    ..In conclusion, we propose a model in which the timing of cell internalization, cell position, and cell sorting combine to determine distinct lineages of the preimplantation mouse embryo. ..
  8. 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. ..
  9. Laitinen M, Anttonen M, Ketola I, Wilson D, Ritvos O, Butzow R, et al. Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors. J Clin Endocrinol Metab. 2000;85:3476-83 pubmed
    ..Our findings support a role for GATA-binding proteins in human ovarian folliculogenesis. Moreover, these data suggest that GATA factors may contribute to the phenotypes of sex cord-derived ovarian tumors...

More Information


  1. Ketola I, Otonkoski T, Pulkkinen M, Niemi H, Palgi J, Jacobsen C, et al. Transcription factor GATA-6 is expressed in the endocrine and GATA-4 in the exocrine pancreas. Mol Cell Endocrinol. 2004;226:51-7 pubmed
    ..We conclude that GATA-4 is a marker of exocrine pancreatic differentiation, whereas GATA-6 is a marker of endocrine pancreatic development...
  2. Kiiveri S, Liu J, Heikkila P, Arola J, Lehtonen E, Voutilainen R, et al. Transcription factors GATA-4 and GATA-6 in human adrenocortical tumors. Endocr Res. 2004;30:919-23 pubmed
    ..GATA expression patterns similar to the animal models can thus be observed in human adrenocortical tumors, but the pathophysiological significance of these findings remains to be elucidated. ..
  3. Caslini C, Capo chichi C, Roland I, Nicolas E, Yeung A, Xu X. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene. 2006;25:5446-61 pubmed
  4. Sodhi C, Li J, Duncan S. Generation of mice harbouring a conditional loss-of-function allele of Gata6. BMC Dev Biol. 2006;6:19 pubmed
    ..This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology. ..
  5. Decker K, Goldman D, Grasch C, Sussel L. Gata6 is an important regulator of mouse pancreas development. Dev Biol. 2006;298:415-29 pubmed
    ..Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests that Gata6 is an important regulator of pancreas specification. ..
  6. Zhou B, Francis T, Yang H, Tseng W, Zhong Q, Frenkel B, et al. GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1. Am J Physiol Cell Physiol. 2008;295:C1141-50 pubmed publisher
    ..These results suggest that transcriptional activation of AQP5 by GATA-6 is mediated at least in part through cooperative interactions with Sp1 occurring at the proximal promoter. ..
  7. Morrisey E, Tang Z, Sigrist K, Lu M, Jiang F, Ip H, et al. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev. 1998;12:3579-90 pubmed
    ..In addition, these data demonstrate that GATA6 is required for establishment of the endodermally derived bronchial epithelium. ..
  8. Perlman H, Suzuki E, Simonson M, Smith R, Walsh K. GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest. J Biol Chem. 1998;273:13713-8 pubmed
    ..In contrast to p53-deficient MEFs and VSMCs, MEFs null for both p21 alleles were refractory to the GATA-6-induced growth inhibition. These data demonstrate that elevated GATA-6 expression can promote the quiescent phenotype in VSMCs. ..
  9. Fitzgerald K, Bazar L, Avigan M. GATA-6 stimulates a cell line-specific activation element in the human lactase promoter. Am J Physiol. 1998;274:G314-24 pubmed
    ..These studies are consistent with an important role of an intestinal GATA binding protein in cell type-specific transactivation of the LPH promoter. ..
  10. Allen H, Flanagan S, Shaw Smith C, De Franco E, Akerman I, Caswell R, et al. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet. 2011;44:20-22 pubmed publisher
    ..These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development. ..
  11. Morrisey E, Ip H, Lu M, Parmacek M. GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Dev Biol. 1996;177:309-22 pubmed
  12. Laverriere A, MacNeill C, Mueller C, Poelmann R, Burch J, Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994;269:23177-84 pubmed
    ..These studies thus provide novel insights into tissue-specific regulation by GATA-5, as well as into possibly overlapping regulatory functions for these three family members. ..
  13. Schrode N, Saiz N, Di Talia S, Hadjantonakis A. GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Dev Cell. 2014;29:454-67 pubmed publisher
    ..This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification. ..
  14. Afouda B, Martin J, Liu F, Ciau Uitz A, Patient R, Hoppler S. GATA transcription factors integrate Wnt signalling during heart development. Development. 2008;135:3185-90 pubmed publisher
    ..These results demonstrate that GATA factors occupy a central position between canonical and non-canonical Wnt signalling in regulating heart muscle formation. ..
  15. Alexandrovich A, Qureishi A, Coudert A, Zhang L, Grigoriadis A, Shah A, et al. A role for GATA-6 in vertebrate chondrogenesis. Dev Biol. 2008;314:457-70 pubmed publisher
    ..These data therefore suggest that GATA-6 also plays a role in chondrogenesis and that Gpr49 is a potential direct target of GATA regulation in this process. ..
  16. Maitra M, Koenig S, Srivastava D, Garg V. Identification of GATA6 sequence variants in patients with congenital heart defects. Pediatr Res. 2010;68:281-5 pubmed publisher
    ..These data suggest that nonsynonymous GATA6 sequence variants are infrequently found in individuals with CHD. ..
  17. 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. ..
  18. Frankenberg S, Gerbe F, Bessonnard S, Belville C, Pouchin P, Bardot O, et al. Primitive endoderm differentiates via a three-step mechanism involving Nanog and RTK signaling. Dev Cell. 2011;21:1005-13 pubmed publisher
    ..Thus, our results reveal three distinct phases in the PrE differentiation program. ..
  19. De Franco E, Shaw Smith C, Flanagan S, Shepherd M, Hattersley A, Ellard S. GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency. Diabetes. 2013;62:993-7 pubmed publisher
    ..Heterozygous GATA6 mutations cause a wide spectrum of diabetes manifestations, ranging from pancreatic agenesis to adult-onset diabetes with subclinical or no exocrine insufficiency. ..
  20. Lepore J, Cappola T, Mericko P, Morrisey E, Parmacek M. GATA-6 regulates genes promoting synthetic functions in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2005;25:309-14 pubmed
    ..The endothelin-1 and the AT1a receptor genes were shown to be direct GATA-6 target genes. These data suggest that GATA-6 plays a role in promoting synthetic functions in VSMCs. ..
  21. Capo Chichi C, Roland I, Vanderveer L, Bao R, Yamagata T, Hirai H, et al. Anomalous expression of epithelial differentiation-determining GATA factors in ovarian tumorigenesis. Cancer Res. 2003;63:4967-77 pubmed
    ..We propose that alterations of GATA transcription factor expression and aberrant nucleocytoplasmic localization may contribute to the anomalous epithelial dedifferentiation of the ovarian tumor cells. ..
  22. 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. ..
  23. Fujikura J, Yamato E, Yonemura S, Hosoda K, Masui S, Nakao K, et al. Differentiation of embryonic stem cells is induced by GATA factors. Genes Dev. 2002;16:784-9 pubmed
    ..We believe that this is the first report of a physiological differentiation event induced by the ectopic expression of a transcription factor in ES cells. ..
  24. Koutsourakis M, Keijzer R, Visser P, Post M, Tibboel D, Grosveld F. Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression. Mech Dev. 2001;105:105-14 pubmed
    ..Thus, elevated levels of GATA6 protein affect early lung development and in analogy to other GATA factors in other tissues, GATA6 also plays a crucial role in the terminal differentiation in this case of the distal pulmonary epithelium. ..
  25. Tamura S, Wang X, Maeda M, Futai M. Gastric DNA-binding proteins recognize upstream sequence motifs of parietal cell-specific genes. Proc Natl Acad Sci U S A. 1993;90:10876-80 pubmed
    ..These results clearly suggest that GATA-GT1 and GATA-GT2 are involved in gene regulation specifically in the gastric epithelium and represent two additional members of the GATA-binding protein family. ..
  26. Suzuki E, Evans T, Lowry J, Truong L, Bell D, Testa J, et al. The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals. Genomics. 1996;38:283-90 pubmed
    ..These data demonstrate that GATA-6 is subject to both tissue-specific and mitogen-responsive regulatory signals. GATA-6 is a prime candidate for a gene that might regulate the differentiative state of VSMCs. ..
  27. Rodriguez A, Allegrucci C, Alberio R. Modulation of pluripotency in the porcine embryo and iPS cells. PLoS ONE. 2012;7:e49079 pubmed publisher
    ..These improved culture conditions will pave the way for the generation of germline competent stem cells in this species...
  28. Kuijk E, van Tol L, Van De Velde H, Wubbolts R, Welling M, Geijsen N, et al. The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos. Development. 2012;139:871-82 pubmed publisher
    ..These findings demonstrate intrinsic differences in early mammalian development in the role of the FGF/MAP kinase signaling pathways in governing hypoblast versus epiblast lineage choices...
  29. Artus J, Panthier J, Hadjantonakis A. A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst. Development. 2010;137:3361-72 pubmed publisher
    ..Taken together, our data suggest a role for PDGF signaling in the expansion of the ExEn lineage. Our observations also uncover a possible role for the PrE in regulating the size of the pluripotent EPI compartment. ..
  30. Wada H, Hasegawa K, Morimoto T, Kakita T, Yanazume T, Sasayama S. A p300 protein as a coactivator of GATA-6 in the transcription of the smooth muscle-myosin heavy chain gene. J Biol Chem. 2000;275:25330-5 pubmed
  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. Wada H, Abe M, Ono K, Morimoto T, Kawamura T, Takaya T, et al. Statins activate GATA-6 and induce differentiated vascular smooth muscle cells. Biochem Biophys Res Commun. 2008;374:731-6 pubmed publisher
    ..These findings suggest that statins activate GATA-6 and induce differentiated VSMCs. ..
  33. Liu C, Glasser S, Wan H, Whitsett J. GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression. J Biol Chem. 2002;277:4519-25 pubmed
    ..GATA-6 influenced the activity of the sp-C promoter, binding and acting synergistically with TTF-1. ..
  34. Pikkarainen S, Tokola H, Kerkela R, Ruskoaho H. GATA transcription factors in the developing and adult heart. Cardiovasc Res. 2004;63:196-207 pubmed
    ..The present review discusses current evidence of the role and regulation of GATA transcription factors in the heart, with an emphasis in the GATA-4 and development of cardiac hypertrophy. ..
  35. Zhao R, Watt A, Li J, Luebke Wheeler J, Morrisey E, Duncan S. GATA6 is essential for embryonic development of the liver but dispensable for early heart formation. Mol Cell Biol. 2005;25:2622-31 pubmed
    ..Our data support the proposal that GATA4 and GATA6 are functionally redundant during hepatic specification but that GATA6 alone is available for liver bud growth and commitment of the endoderm to a hepatic cell fate. ..
  36. Maeda M, Ohashi K, Ohashi Kobayashi A. Further extension of mammalian GATA-6. Dev Growth Differ. 2005;47:591-600 pubmed
  37. 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. ..
  38. Narita N, Heikinheimo M, Bielinska M, White R, Wilson D. The gene for transcription factor GATA-6 resides on mouse chromosome 18 and is expressed in myocardium and vascular smooth muscle. Genomics. 1996;36:345-8 pubmed
    ..The presence of GATA-6 mRNA in vascular smooth muscle suggests that this transcription factor may play a distinctive role in gene expression in this cell type. ..
  39. 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. ..
  40. Kanematsu A, Ramachandran A, Adam R. GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating alpha-smooth muscle actin gene expression. Am J Physiol Cell Physiol. 2007;293:C1093-102 pubmed
    ..In addition, these findings demonstrate that GATA-6 regulates human alpha-SMA expression via a novel regulatory cis element in the alpha-SMA promoter-enhancer. ..
  41. Wood J, Nelson V, Ho C, Jansen E, Wang C, Urbanek M, et al. The molecular phenotype of polycystic ovary syndrome (PCOS) theca cells and new candidate PCOS genes defined by microarray analysis. J Biol Chem. 2003;278:26380-90 pubmed
  42. Barbuti A, Galvez B, Crespi A, Scavone A, Baruscotti M, Brioschi C, et al. Mesoangioblasts from ventricular vessels can differentiate in vitro into cardiac myocytes with sinoatrial-like properties. J Mol Cell Cardiol. 2010;48:415-23 pubmed publisher
    ..These data represent the first evidence for in vitro generation of pacemaker-like myocytes from proliferating non-embryonic stem/progenitor cells. ..
  43. Kiiveri S, Liu J, Westerholm Ormio M, Narita N, Wilson D, Voutilainen R, et al. Differential expression of GATA-4 and GATA-6 in fetal and adult mouse and human adrenal tissue. Endocrinology. 2002;143:3136-43 pubmed
    ..GATA-4, on the other hand, may serve a role in the fetal adrenal gene regulation, although it is not essential for early adrenocortical differentiation. ..
  44. Keijzer R, van Tuyl M, Meijers C, Post M, Tibboel D, Grosveld F, et al. The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development. Development. 2001;128:503-11 pubmed
    ..Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation. ..
  45. Futaki S, Hayashi Y, Emoto T, Weber C, Sekiguchi K. Sox7 plays crucial roles in parietal endoderm differentiation in F9 embryonal carcinoma cells through regulating Gata-4 and Gata-6 expression. Mol Cell Biol. 2004;24:10492-503 pubmed
    ..Sox7 is therefore required for the induction of Gata-4 and Gata-6, and the interplay among these transcription factors plays a crucial role in parietal endoderm differentiation. ..
  46. Shureiqi I, Jiang W, Fischer S, Xu X, Chen D, Lee J, et al. GATA-6 transcriptional regulation of 15-lipoxygenase-1 during NSAID-induced apoptosis in colorectal cancer cells. Cancer Res. 2002;62:1178-83 pubmed
    ..Ectopic GATA-6 expression blocked NSAID induction of 15-LOX-1 and apoptosis. NSAIDs down-regulate GATA-6 to transcriptionally up-regulate 15-LOX-1 and induce apoptosis in colorectal cancer cells. ..
  47. Kodo K, Nishizawa T, Furutani M, Arai S, Yamamura E, Joo K, et al. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling. Proc Natl Acad Sci U S A. 2009;106:13933-8 pubmed publisher
    ..Together, our data implicate mutations in GATA6 as genetic causes of CHD involving OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling. ..
  48. 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
  49. 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. ..
  50. Kuo C, Morrisey E, Anandappa R, Sigrist K, Lu M, Parmacek M, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11:1048-60 pubmed
    ..However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis. ..
  51. Dimaline R, Campbell B, Watson F, Sandvik A, Struthers J, Noble P. Regulated expression of GATA-6 transcription factor in gastric endocrine cells. Gastroenterology. 1997;112:1559-67 pubmed
    ..The aim of this study was to determine if GATA factors are located in gastric endocrine cells and to examine their expression during development and in response to changes in the gastric luminal environment...
  52. 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. ..
  53. Haveri H, Westerholm Ormio M, Lindfors K, Maki M, Savilahti E, Andersson L, et al. Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa. BMC Gastroenterol. 2008;8:9 pubmed publisher
    ..Furthermore, GATA-4, GATA-6 and Ihh expression is altered in premalignant dysplastic lesions and reduced in overt cancer. ..