“GATA4”的意思、由来-开放百科全书

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]

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.^[8]

Atrioventricular valve formation

GATA4 expression during cardiac development has been shown to be essential to proper atrioventricular (AV) formation and function.^[9] 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.^[9] 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.^[9] 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.^[9] 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.^[9]

Interactions

GATA4 has been shown to interact with NKX2-5,^[10]^[11]^[12] TBX5,^[13] Serum response factor^[14]^[15] HAND2,^[16] and HDAC2.^[17]

Clinical relevance

Mutations in this gene have been associated to cases of congenital diaphragmatic hernia.^[18] Atrial septal defects, tetralogy of Fallot, and ventricular septal defects associated with GATA4 mutation were also seen in South Indian patients.^[19]

See also

References

1. ^{{cite journal |vauthors=White RA, Dowler LL, Pasztor LM, Gatson LL, Adkison LR, Angeloni SV, Wilson DB | title = Assignment of the transcription factor GATA4 gene to human chromosome 8 and mouse chromosome 14: Gata4 is a candidate gene for Ds (disorganization) | journal = Genomics | volume = 27 | issue = 1 | pages = 20–6 |date=October 1995 | pmid = 7665171 | pmc = | doi = 10.1006/geno.1995.1003 }}
2. ^{{cite web | title = Entrez Gene: GATA4 GATA binding protein 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2626| accessdate = }}
3. ^{{cite journal |vauthors=Köhler B, Lin L, Ferraz-de-Souza B, Wieacker P, Heidemann P, Schröder V, Biebermann H, Schnabel D, Grüters A, Achermann JC | title = Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency | journal = Hum. Mutat. | volume = 29 | issue = 1 | pages = 59–64 |date=January 2008 | pmid = 17694559 | pmc = 2359628 | doi = 10.1002/humu.20588 }}
4. ^¹[Perrino, Cinzia and Rockman, Howard A. GATA4 and the two sides of gene expression reprogramming. 2006. Circulation Research, 98: 837-845.]
5. ^{{cite journal | vauthors = Black BL, McCulley DJ | year = | title = Transcription factor pathways and congenital heart disease. 2012 | url = | journal = Current Topics in Developmental Biology | volume = 100 | issue = | pages = 253–277 }}
6. ^{{cite journal | vauthors = Zhou P et al | year = | title = Regulation of GATA4 transcriptional activity in cardiovascular development and disease. 2012 | url = | journal = Current Topics in Developmental Biology | volume = 100 | issue = | pages = 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. ^{{cite journal | vauthors = Cao X, Li M | year = 2015 | title = A New Pathway for Senescence Regulation | url = | journal = Genomics, Proteomics & Bioinformatics | volume = 13 | issue = 6| pages = 333–335 | doi=10.1016/j.gpb.2015.11.002}}
9. ^¹²³⁴⁵{{cite journal|last1=Rivera-Feliciano|first1=Jose|author2=Kyu-Ho Lee|author3=Sek Won Kong|author4=Satish Rajagopal|author5=Qing Ma|author6=Zhangli Springer|author7=Seigo Izumo|author8=Clifford J. Tabin|author9=William T. Pu|title=Development of heart valves requires GATA4 expression in endothelial-derived cells|journal=Development|date=September 15, 2006|volume=133|pages=3607–3618|doi=10.1242/dev.02519|url=http://dev.biologists.org/content/133/18/3607.full?sid=92820735-6286-4362-8497-c411fe5a0225#cited-by|accessdate=13 April 2015|pmid=16914500|pmc=2735081}}
10. ^{{cite journal |vauthors=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 | title = GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5 | journal = Nature | volume = 424 | issue = 6947 | pages = 443–7 |date=July 2003 | pmid = 12845333 | doi = 10.1038/nature01827 }}
11. ^{{cite journal |vauthors=Durocher D, Charron F, Warren R, Schwartz RJ, Nemer M | title = The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors | journal = EMBO J. | volume = 16 | issue = 18 | pages = 5687–96 |date=September 1997 | pmid = 9312027 | pmc = 1170200 | doi = 10.1093/emboj/16.18.5687 }}
12. ^{{cite journal |vauthors=Zhu W, Shiojima I, Hiroi Y, Zou Y, Akazawa H, Mizukami M, Toko H, Yazaki Y, Nagai R, Komuro I | title = Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease | journal = J. Biol. Chem. | volume = 275 | issue = 45 | pages = 35291–6 |date=November 2000 | pmid = 10948187 | doi = 10.1074/jbc.M000525200 }}
13. ^{{cite journal |vauthors=Svensson EC, Tufts RL, Polk CE, Leiden JM | title = Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 3 | pages = 956–61 |date=February 1999 | pmid = 9927675 | pmc = 15332 | doi = 10.1073/pnas.96.3.956 }}
14. ^{{cite journal |vauthors=Belaguli NS, Sepulveda JL, Nigam V, Charron F, Nemer M, Schwartz RJ | title = Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators | journal = Mol. Cell. Biol. | volume = 20 | issue = 20 | pages = 7550–8 |date=October 2000 | pmid = 11003651 | pmc = 86307 | doi = 10.1128/MCB.20.20.7550-7558.2000 }}
15. ^{{cite journal |vauthors=Morin S, Paradis P, Aries A, Nemer M | title = Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor | journal = Mol. Cell. Biol. | volume = 21 | issue = 4 | pages = 1036–44 |date=February 2001 | pmid = 11158291 | pmc = 99558 | doi = 10.1128/MCB.21.4.1036-1044.2001 }}
16. ^{{cite journal |vauthors=Dai YS, Cserjesi P, Markham BE, Molkentin JD | title = The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism | journal = J. Biol. Chem. | volume = 277 | issue = 27 | pages = 24390–8 |date=July 2002 | pmid = 11994297 | doi = 10.1074/jbc.M202490200 }}
17. ^{{cite journal |vauthors=Trivedi CM, Zhu W, Wang Q, Jia C, Kee HJ, Li L, Hannenhalli S, Epstein JA | title = Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation | journal = Dev. Cell | volume = 19 | issue = 3 | pages = 450–9 |date=September 2010 | pmid = 20833366 | pmc = 2947937 | doi = 10.1016/j.devcel.2010.08.012 | laysummary = http://www.physorg.com/news205686730.html | laysource = Phys.Org }}
18. ^{{cite journal |vauthors=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 | title = Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia | journal = Hum. Genet. | volume = 132| issue = 3| pages = 285–92|date=November 2012 | pmid = 23138528 | doi = 10.1007/s00439-012-1249-0 | pmc = 3570587}}
19. ^{{cite journal |vauthors=Mattapally S, Nizamuddin S, Murthy KS, Thangaraj K, Banerjee SK | title = c.620C>T mutation in GATA4 is associated with congenital heart disease in South India | journal = BMC Med. Genet. | volume = 16| issue = 1| pages = 7|date=December 2015 | pmid = 25928801 | doi = 10.1186/s12881-015-0152-7 }}

Function

Atrioventricular valve formation

Interactions

Clinical relevance

See also

References

Further reading

External links