GATA6 explained

Transcription factor GATA-6, also known as GATA-binding factor 6 (GATA6), is protein that in humans is encoded by the GATA6 gene.^[1] The gene product preferentially binds (A/T/C)GAT(A/T)(A) of the consensus binding sequence.^[2]

Clinical significance

Mutations in the gene have been linked with pancreatic agenesis and congenital heart defects.^[3]

Lung Endodermal Epithelial Development

GATA-6, a zinc finger transcription factor, is important in the endodermal differentiation of organ tissues.^[4] It is also indicated in proper lung development by controlling the late differentiation stages of alveolar epithelium and aquaporin-5 promoter activation. Furthermore, GATA-6 has been linked to the production of LIF, a cytokine that encourages proliferation of endodermal embryonic stem cells and blocks early epiblast differentiation. If left unregulated in the developing embryo, this cytokine production and chemical signal contributes to the phenotypes discussed further below.^[5]

Upon the disruption of GATA-6 in an embryo, the distal lung epithelial development is stunted in transgenic mice models The progenitor cells, or stem cells, for alveolar epithelial tissues develop and are specified appropriately, however further differentiation does not occur. Also the distal-proximal bronchiole development is affected, resulting in a reduced quantity of airway exchange sites.

This branching deficit, which will cause bilateral pulmonary hypoplasia after birth, has been locally associated with areas lacking differentiated alveolar epithelium, implicating this phenotype as inherent to endodermal function, and thus may be indirectly linked to improper GATA-6 expression.^{[6] [7]} That is, a deficit of bronchiole branching may not be a result of direct transcriptional error in GATA-6, but rather a side effect of such an error.

See also

• GATA transcription factor

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki E, Evans T, Lowry J, Truong L, Bell DW, Testa JR, Walsh K . The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals . Genomics . 38 . 3 . 283–90 . 1997 . 8975704 . 10.1006/geno.1996.0630 .
• Huggon IC, Davies A, Gove C, Moscoso G, Moniz C, Foss Y, Farzaneh F, Towner P . Molecular cloning of human GATA-6 DNA binding protein: high levels of expression in heart and gut . Biochim. Biophys. Acta . 1353 . 2 . 98–102 . 1997 . 9294001 . 10.1016/s0167-4781(97)00049-3 .
• Yoshida T, Sato R, Mahmood S, Kawasaki S, Futai M, Maeda M . GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45 cells . FEBS Lett. . 414 . 2 . 333–7 . 1997 . 9315713 . 10.1016/S0014-5793(97)01017-X . 31858845 . free . 1997FEBSL.414..333Y .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• 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. . 275 . 33 . 25330–5 . 2000 . 10851229 . 10.1074/jbc.M000828200 . free .
• Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK . Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors . J. Biol. Chem. . 277 . 5 . 3585–92 . 2002 . 11724781 . 10.1074/jbc.M107995200 . free .
• Liu C, Glasser SW, Wan H, Whitsett JA . GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression . J. Biol. Chem. . 277 . 6 . 4519–25 . 2002 . 11733512 . 10.1074/jbc.M107585200 . free .
• Kiiveri S, Liu J, Westerholm-Ormio M, Narita N, Wilson DB, Voutilainen R, Heikinheimo M . Transcription factors GATA-4 and GATA-6 during mouse and human adrenocortical development . Endocr. Res. . 28 . 4 . 647–50 . 2003 . 12530677 . 10.1081/ERC-120016980 . 22011163 .
• Chang DF, Belaguli NS, Iyer D, Roberts WB, Wu SP, Dong XR, Marx JG, Moore MS, Beckerle MC, Majesky MW, Schwartz RJ . Cysteine-rich LIM-only proteins CRP1 and CRP2 are potent smooth muscle differentiation cofactors . Dev. Cell . 4 . 1 . 107–18 . 2003 . 12530967 . 10.1016/S1534-5807(02)00396-9 . free .
• Nemer G, Nemer M . Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6 . Dev. Biol. . 254 . 1 . 131–48 . 2003 . 12606287 . 10.1016/S0012-1606(02)00026-X .
• Abe M, Hasegawa K, Wada H, Morimoto T, Yanazume T, Kawamura T, Hirai M, Furukawa Y, Kita T . GATA-6 is involved in PPARgamma-mediated activation of differentiated phenotype in human vascular smooth muscle cells . Arterioscler. Thromb. Vasc. Biol. . 23 . 3 . 404–10 . 2003 . 12615657 . 10.1161/01.ATV.0000059405.51042.A0 . free . 2433/147514 . free .
• Ketola I, Toppari J, Vaskivuo T, Herva R, Tapanainen JS, Heikinheimo M . Transcription factor GATA-6, cell proliferation, apoptosis, and apoptosis-related proteins Bcl-2 and Bax in human fetal testis . J. Clin. Endocrinol. Metab. . 88 . 4 . 1858–65 . 2003 . 12679484 . 10.1210/jc.2002-021647 . free .
• Siltanen S, Heikkilä P, Bielinska M, Wilson DB, Heikinheimo M . Transcription factor GATA-6 is expressed in malignant endoderm of pediatric yolk sac tumors and in teratomas . Pediatr. Res. . 54 . 4 . 542–6 . 2004 . 12867597 . 10.1203/01.PDR.0000081295.56529.E9 . free .
• Liu C, Ikegami M, Stahlman MT, Dey CR, Whitsett JA . Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6 . Am. J. Physiol. Lung Cell Mol. Physiol. . 285 . 6 . L1246–54 . 2003 . 12909592 . 10.1152/ajplung.00443.2002 .
• Benchabane H, Wrana JL . GATA- and Smad1-Dependent Enhancers in the Smad7 Gene Differentially Interpret Bone Morphogenetic Protein Concentrations . Mol. Cell. Biol. . 23 . 18 . 6646–61 . 2003 . 12944489 . 193708 . 10.1128/MCB.23.18.6646-6661.2003 .
• Jimenez P, Saner K, Mayhew B, Rainey WE . GATA-6 is expressed in the human adrenal and regulates transcription of genes required for adrenal androgen biosynthesis . Endocrinology . 144 . 10 . 4285–8 . 2003 . 12959982 . 10.1210/en.2003-0472 . free .
• Saner KJ, Suzuki T, Sasano H, Pizzey J, Ho C, Strauss JF, Carr BR, Rainey WE . Steroid sulfotransferase 2A1 gene transcription is regulated by steroidogenic factor 1 and GATA-6 in the human adrenal . Mol. Endocrinol. . 19 . 1 . 184–97 . 2005 . 15388788 . 10.1210/me.2003-0332 . free .
• Kiiveri S, Liu J, Heikkilä P, Arola J, Lehtonen E, Voutilainen R, Heikinheimo M . Transcription factors GATA-4 and GATA-6 in human adrenocortical tumors . Endocr. Res. . 30 . 4 . 919–23 . 2005 . 15666845 . 10.1081/ERC-200044149 . 27526305 .

Notes and References

1. Web site: Entrez Gene: GATA6 GATA binding protein 6.
2. Sakai Y, Nakagawa R, Sato R, Maeda M . Selection of DNA binding sites for human transcriptional regulator GATA-6. . Biochem Biophys Res Commun . 250 . 3 . 682–688 . 1998 . 10.1006/bbrc.1998.9374 . 9784406 .
3. Chao CS, McKnight KD, Cox KL, Chang AL, Kim SK, Feldman BJ . Novel GATA6 Mutations in Patients with Pancreatic Agenesis and Congenital Heart Malformations . PLOS ONE . 10 . 2 . e0118449 . 2015 . 25706805 . 10.1371/journal.pone.0118449 . 4338276. 2015PLoSO..1018449C . free .
4. Yang H, Lu MM, Zhang L, Whitsett JA, Morrisey EE . GATA6 regulates differentiation of distal lung epithelium . Development . 129 . 9 . 2233–46 . May 2002 . 10.1242/dev.129.9.2233 . 11959831 .
5. Morgani SM, Brickman JM . LIF supports primitive endoderm expansion during pre-implantation development . Development . 142 . 20 . 3488–99 . October 2015 . 26395492 . 10.1242/dev.125021 . free . 20.500.11820/9c72866a-3d10-4e07-89eb-1c0bb12a18e5 . free .
6. Keijzer R, van Tuyl M, Meijers C, Post M, Tibboel D, Grosveld F, Koutsourakis M . The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development . Development . 128 . 4 . 503–11 . February 2001 . 10.1242/dev.128.4.503 . 11171334 . 1765/9590 . free .
7. Book: Rennie, Janet . Rennie & Robertson's Textbook on Neonatology . vanc . Elsevier Health Sciences . 2012 . 978-0-7020-3479-4 .