GATA4
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| Location (UCSC) | Chr 8: 11.68 – 11.76 Mb | Chr 14: 63.44 – 63.51 Mb | |||||||
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Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.[5]
Function
This gene encodes a member of the GATA family of zinc finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function. Mutations in this gene have been associated with cardiac septal defects as well as reproductive defects.[6][7]
GATA4 is a critical transcription factor for proper mammalian cardiac development and essential for survival of the embryo. GATA4 works in combination with other essential cardiac transcription factors as well, such as Nkx2-5 and Tbx5. GATA4 is expressed in both embryo and adult cardiomyocytes where it functions as a transcriptional regulator for many cardiac genes, and also regulates hypertrophic growth of the heart.[8] GATA4 promotes cardiac morphogenesis, cardiomyocytes survival, and maintains cardiac function in the adult heart.[8] Mutations or defects in the GATA4 gene can lead to a variety of cardiac problems including congenital heart disease, abnormal ventral folding, and defects in the cardiac septum separating the atria and ventricles, and hypoplasia of the ventricular myocardium.[9] As seen from the abnormalities from deletion of GATA4, it is essential for cardiac formation and the survival of the embryo during fetal development.[10] GATA4 is not only important for cardiac development, but also development and function of the mammalian fetal ovary and contributes to fetal male gonadal development and mutations may lead to defects in reproductive development. GATA4 has also been discovered to have an integral role in controlling the early stages of pancreatic and hepatic development.[8]
GATA4 is regulated through the autophagy-lysosome pathway in eukaryotic cells. In cellular senescence, ATM and ATR inhibit p62, an autophagy adaptor responsible for selective autophagy of GATA4. Inhibition of p62 leads to increased GATA4 levels, resulting in NF-kB activation and subsequent SASP induction.[11][12]
Atrioventricular valve formation
GATA4 expression during cardiac development has been shown to be essential to proper atrioventricular (AV) formation and function.[13] Endocardial cells undergo epithelial to mesenchymal transitions (EMT) into the AV cushions during development. Their proliferation and fusion leads to division of the ventricular inlet into two different passageways with two AV valves, and they are thought to be under the influence of the GATA4 transcription factor.[13] GATA4 inactivation, with GATA4-null mice, leads to down regulation of Erbb3 and altered Erk expression, two other important molecules in EMT and ventricular inlet separation.[13] This has been shown to lead to pericardial effusion and peripheral hemorrhage in E12.5 mice, which succumb due to heart failure before weaning age.[13] This data could have important implications for human medicine by suggesting that mutations with the GATA4 transcription factor could be responsible for AV cushion defects in humans with improper septal formation leading to congenital heart disease.[13]
Interactions
GATA4 has been shown to
GATA4 has also been shown to interact with Erbb3, FOG-1, and FOG-2.[13]
Clinical relevance
Mutations in this gene have been associated to cases of congenital diaphragmatic hernia.[22] Atrial septal defects, tetralogy of Fallot, and ventricular septal defects associated with GATA4 mutation were also seen in South Indian patients.[23]
See also
References
- ^ a b c ENSG00000285109 GRCh38: Ensembl release 89: ENSG00000136574, ENSG00000285109 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021944 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7665171.
- ^ "Entrez Gene: GATA4 GATA binding protein 4".
- PMID 17694559.
- ^ S2CID 18985950.
- PMID 22449847.
- PMID 22449843.
- PMID 26777575.
- PMID 26404840.
- ^ PMID 16914500.
- S2CID 4304709.
- PMID 9312027.
- PMID 10948187.
- PMID 9927675.
- PMID 11003651.
- PMID 11158291.
- PMID 11994297.
- PMID 20833366.
- Lay summary in: "Three-way control of fetal heart-cell proliferation could help regenerate cardiac cells". Phys.Org. October 7, 2010.
- PMID 23138528.
- PMID 25928801.
Further reading
- Evans T, Reitman M, Felsenfeld G (1988). "An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes". Proc. Natl. Acad. Sci. U.S.A. 85 (16): 5976–80. PMID 3413070.
- Huang WY, Cukerman E, Liew CC (1995). "Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding gene and isolation of a human GATA-4 cDNA". Gene. 155 (2): 219–23. PMID 7721094.
- Yamagata T, Nishida J, Sakai R, et al. (1995). "Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins". Mol. Cell. Biol. 15 (7): 3830–9. PMID 7791790.
- Molkentin JD, Kalvakolanu DV, Markham BE (1994). "Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene". Mol. Cell. Biol. 14 (7): 4947–57. PMID 8007990.
- Arceci RJ, King AA, Simon MC, et al. (1993). "Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart". Mol. Cell. Biol. 13 (4): 2235–46. PMID 8455608.
- Huang WY, Heng HH, Liew CC (1997). "Assignment of the human GATA4 gene to 8p23.1→p22 using fluorescence in situ hybridization analysis". Cytogenet. Cell Genet. 72 (2–3): 217–8. PMID 8978781.
- Herzig TC, Jobe SM, Aoki H, et al. (1997). "Angiotensin II type1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7543–8. PMID 9207128.
- Durocher D, Charron F, Warren R, et al. (1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". EMBO J. 16 (18): 5687–96. PMID 9312027.
- Molkentin JD, Lu JR, Antos CL, et al. (1998). "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy". Cell. 93 (2): 215–28. PMID 9568714.
- Svensson EC, Tufts RL, Polk CE, Leiden JM (1999). "Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes". Proc. Natl. Acad. Sci. U.S.A. 96 (3): 956–61. PMID 9927675.
- Tremblay JJ, Viger RS (1999). "Transcription factor GATA-4 enhances Müllerian inhibiting substance gene transcription through a direct interaction with the nuclear receptor SF-1". Mol. Endocrinol. 13 (8): 1388–401. S2CID 22242126.
- Lin L, Aggarwal S, Glover TW, et al. (2000). "A minimal critical region of the 8p22-23 amplicon in esophageal adenocarcinomas defined using sequence tagged site-amplification mapping and quantitative polymerase chain reaction includes the GATA-4 gene". Cancer Res. 60 (5): 1341–7. PMID 10728696.
- Morin S, Charron F, Robitaille L, Nemer M (2000). "GATA-dependent recruitment of MEF2 proteins to target promoters". EMBO J. 19 (9): 2046–55. PMID 10790371.
- Zhu W, Shiojima I, Hiroi Y, et al. (2001). "Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease". J. Biol. Chem. 275 (45): 35291–6. PMID 10948187.
- Belaguli NS, Sepulveda JL, Nigam V, et al. (2000). "Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators". Mol. Cell. Biol. 20 (20): 7550–8. PMID 11003651.
- Morin S, Paradis P, Aries A, Nemer M (2001). "Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor". Mol. Cell. Biol. 21 (4): 1036–44. PMID 11158291.
- Crispino JD, Lodish MB, Thurberg BL, et al. (2001). "Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors". Genes Dev. 15 (7): 839–44. PMID 11297508.
- Dai YS, Markham BE (2001). "p300 Functions as a coactivator of transcription factor GATA-4". J. Biol. Chem. 276 (40): 37178–85. PMID 11481322.
- Liang Q, Wiese RJ, Bueno OF, et al. (2001). "The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes". Mol. Cell. Biol. 21 (21): 7460–9. PMID 11585926.
External links
- GATA4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P43694 (Transcription factor GATA-4) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.