GATA4

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GATA binding protein 4
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GATA4 ; ASD2; TACHD; VSD1
External IDs OMIM600576 MGI95664 HomoloGene1551 ChEMBL: 1687679 GeneCards: GATA4 Gene
RNA expression pattern
PBB GE GATA4 205517 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2626 14463
Ensembl ENSG00000136574 ENSMUSG00000021944
UniProt P43694 Q08369
RefSeq (mRNA) NM_002052 NM_008092
RefSeq (protein) NP_002043 NP_032118
Location (UCSC) Chr 8:
11.53 – 11.62 Mb
Chr 14:
63.2 – 63.27 Mb
PubMed search [1] [2]

Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.[1]

Function[edit]

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.[2][3]

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.[4] GATA4 promotes cardiac morphogenesis, cardiomyocytes survival, and maintains cardiac function in the adult heart.[4] 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.[5] As seen from the abnormalities from deletion of GATA4, it is essential for cardiac formation and the survival of the embryo during fetal development.[6] 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.[7]

Interactions[edit]

GATA4 has been shown to interact with NKX2-5,[8][9][10] TBX5,[11] Serum response factor[12][13] HAND2,[14] and HDAC2.[15]

Clinical relevance[edit]

Mutations in this gene have been associated to cases of congenital diaphragmatic hernia.[16]

See also[edit]

References[edit]

  1. ^ White RA, Dowler LL, Pasztor LM, Gatson LL, Adkison LR, Angeloni SV, Wilson DB (October 1995). "Assignment of the transcription factor GATA4 gene to human chromosome 8 and mouse chromosome 14: Gata4 is a candidate gene for Ds (disorganization)". Genomics 27 (1): 20–6. doi:10.1006/geno.1995.1003. PMID 7665171. 
  2. ^ "Entrez Gene: GATA4 GATA binding protein 4". 
  3. ^ Köhler B, Lin L, Ferraz-de-Souza B, Wieacker P, Heidemann P, Schröder V, Biebermann H, Schnabel D, Grüters A, Achermann JC (January 2008). "Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency". Hum. Mutat. 29 (1): 59–64. doi:10.1002/humu.20588. PMC 2359628. PMID 17694559. 
  4. ^ a b [Perrino, Cinzia and Rockman, Howard A. GATA4 and the two sides of gene expression reprogramming. 2006. Circulation Research, 98: 837-845.]
  5. ^ [Black, Bryan L. and McCulley, David J. Transcription factor pathways and congenital heart disease. 2012. Current Topics in Developmental Biology, 100: 253-277]
  6. ^ [Zhou, Pingzhu, et al. Regulation of GATA4 transcriptional activity in cardiovascular development and disease. 2012. Current Topics in Developmental Biology, 100: 143-169]
  7. ^ [Perrino, Cinzia and Rockman, Howard A. GATA4 and the two sides of gene expression reprogramming. 2006. Circulation Research, 98: 837-845]
  8. ^ Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D (July 2003). "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5". Nature 424 (6947): 443–7. doi:10.1038/nature01827. PMID 12845333. 
  9. ^ Durocher D, Charron F, Warren R, Schwartz RJ, Nemer M (September 1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". EMBO J. 16 (18): 5687–96. doi:10.1093/emboj/16.18.5687. PMC 1170200. PMID 9312027. 
  10. ^ Zhu W, Shiojima I, Hiroi Y, Zou Y, Akazawa H, Mizukami M, Toko H, Yazaki Y, Nagai R, Komuro I (November 2000). "Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease". J. Biol. Chem. 275 (45): 35291–6. doi:10.1074/jbc.M000525200. PMID 10948187. 
  11. ^ Svensson EC, Tufts RL, Polk CE, Leiden JM (February 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. doi:10.1073/pnas.96.3.956. PMC 15332. PMID 9927675. 
  12. ^ Belaguli NS, Sepulveda JL, Nigam V, Charron F, Nemer M, Schwartz RJ (October 2000). "Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators". Mol. Cell. Biol. 20 (20): 7550–8. doi:10.1128/MCB.20.20.7550-7558.2000. PMC 86307. PMID 11003651. 
  13. ^ Morin S, Paradis P, Aries A, Nemer M (February 2001). "Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor". Mol. Cell. Biol. 21 (4): 1036–44. doi:10.1128/MCB.21.4.1036-1044.2001. PMC 99558. PMID 11158291. 
  14. ^ Dai YS, Cserjesi P, Markham BE, Molkentin JD (July 2002). "The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism". J. Biol. Chem. 277 (27): 24390–8. doi:10.1074/jbc.M202490200. PMID 11994297. 
  15. ^ Trivedi CM, Zhu W, Wang Q, Jia C, Kee HJ, Li L, Hannenhalli S, Epstein JA (September 2010). "Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation". Dev. Cell 19 (3): 450–9. doi:10.1016/j.devcel.2010.08.012. PMC 2947937. PMID 20833366. Lay summaryPhys.Org. 
  16. ^ Yu L, Wynn J, Cheung YH, Shen Y, Mychaliska GB, Crombleholme TM, Azarow KS, Lim FY, Chung DH, Potoka D, Warner BW, Bucher B, Stolar C, Aspelund G, Arkovitz MS, Chung WK (November 2012). "Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia". Hum. Genet. 132 (3): 285–92. doi:10.1007/s00439-012-1249-0. PMID 23138528. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.