Transcription factor GATA-6, also known asGATA-binding factor 6 (GATA6), isprotein that in humans is encoded by theGATA6gene.[5] The gene product preferentially binds (A/T/C)GAT(A/T)(A) of theconsensus binding sequence.[6]
GATA-6, azinc finger transcription factor, is important in theendodermal differentiation of organ tissues.[8] 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.[9]
Upon the disruption of GATA-6 in an embryo, the distal lung epithelial development is stunted in transgenic mice models[8] Theprogenitor 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.[8]
This branching deficit, which will cause bilateralpulmonary 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.[10][11] 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.
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Suzuki E, Evans T, Lowry J, Truong L, Bell DW, Testa JR, Walsh K (1997). "The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals".Genomics.38 (3):283–90.doi:10.1006/geno.1996.0630.PMID8975704.
Huggon IC, Davies A, Gove C, Moscoso G, Moniz C, Foss Y, Farzaneh F, Towner P (1997). "Molecular cloning of human GATA-6 DNA binding protein: high levels of expression in heart and gut".Biochim. Biophys. Acta.1353 (2):98–102.doi:10.1016/s0167-4781(97)00049-3.PMID9294001.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library".Gene.200 (1–2):149–56.doi:10.1016/S0378-1119(97)00411-3.PMID9373149.
Kiiveri S, Liu J, Westerholm-Ormio M, Narita N, Wilson DB, Voutilainen R, Heikinheimo M (2003). "Transcription factors GATA-4 and GATA-6 during mouse and human adrenocortical development".Endocr. Res.28 (4):647–50.doi:10.1081/ERC-120016980.PMID12530677.S2CID22011163.
Nemer G, Nemer M (2003). "Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6".Dev. Biol.254 (1):131–48.doi:10.1016/S0012-1606(02)00026-X.PMID12606287.
Liu C, Ikegami M, Stahlman MT, Dey CR, Whitsett JA (2003). "Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6".Am. J. Physiol. Lung Cell Mol. Physiol.285 (6): L1246–54.doi:10.1152/ajplung.00443.2002.PMID12909592.
Kiiveri S, Liu J, Heikkilä P, Arola J, Lehtonen E, Voutilainen R, Heikinheimo M (2005). "Transcription factors GATA-4 and GATA-6 in human adrenocortical tumors".Endocr. Res.30 (4):919–23.doi:10.1081/ERC-200044149.PMID15666845.S2CID27526305.
