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GATA Transcription Factors and Cardiovascular Disease

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Heart Genomics

Part of the book series: Translational Bioinformatics ((TRBIO,volume 16))

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Abstract

Development of the mammalian heart is a complex process that involves the specification and differentiation of cardiovascular progenitor cells, their migration to the organ-forming region, interactions and signaling within and between tissues, and later growth and functional maturation of the organ. Normal heart structure and function rely on the precise expression and regulation of the transcription factor network during organogenesis. Over the last three decades, intensive studies from a number of invertebrate and vertebrate species have identified multiple genes encoding cardiac transcription factors, including GATA4/5/6, Nkx2-5, Tbx5, SRF, Mef2c, FOG, and HAND2, which are required for cardiogenesis. Defective expression or interactions between cardiac transcription factors underlie a significant portion of congenital heart disease. In this chapter, we summarize the current understanding of the functions of GATA transcription factors, especially GATA4, GATA5, and GATA6, in cardiovascular development and the molecular interactions of GATA factors with other transcription factors. The association of GATA transcription factors with cardiovascular disease is also discussed.

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References

  • Akazawa H, Komuro I. Roles of cardiac transcription factors in cardiac hypertrophy. Circ Res. 2003;92(10):1079–88.

    Article  CAS  PubMed  Google Scholar 

  • Allen HL, Flanagan SE, Shaw-Smith C, De Franco E, Akerman I, Caswell R, C. International Pancreatic Agenesis, Ferrer J, Hattersley AT, Ellard S. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet. 2011;44(1):20–2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arceci RJ, King AA, Simon MC, Orkin SH, Wilson DB. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993;13(4):2235–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bates DL, Chen Y, Kim G, Guo L, Chen L. Crystal structures of multiple GATA zinc fingers bound to DNA reveal new insights into DNA recognition and self-association by GATA. J Mol Biol. 2008;381(5):1292–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belaguli NS, Sepulveda JL, Nigam V, Charron F, Nemer M, Schwartz RJ. Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators. Mol Cell Biol. 2000;20(20):7550–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bisping E, Ikeda S, Kong SW, Tarnavski O, Bodyak N, McMullen JR, Rajagopal S, Son JK, Ma Q, Springer Z, Kang PM, Izumo S, Pu WT. Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Proc Natl Acad Sci U S A. 2006;103(39):14471–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Marks MH, Walker AJ, Seki T, Oh SP, Lu JT, Sumners C, Raizada MK, Horikoshi N, Weinberg EO, Yasui K, Ikeda Y, Chien KR, Kasahara H. Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res. 2008;103(6):580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brody MJ, Cho E, Mysliwiec MR, Kim TG, Carlson CD, Lee KH, Lee Y. Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4. J Mol Cell Cardiol. 2013;62:237–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown DD, Martz SN, Binder O, Goetz SC, Price BM, Smith JC, Conlon FL. Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis. Development. 2005;132(3):553–63.

    Article  CAS  PubMed  Google Scholar 

  • Cai KQ, Capo-Chichi CD, Rula ME, Yang DH, Xu XX. Dynamic GATA6 expression in primitive endoderm formation and maturation in early mouse embryogenesis. Dev Dyn. 2008;237(10):2820–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantor AB, Orkin SH. Coregulation of GATA factors by the Friend of GATA (FOG) family of multitype zinc finger proteins. Semin Cell Dev Biol. 2005;16(1):117–28.

    Article  CAS  PubMed  Google Scholar 

  • Carter DR, Buckle AD, Tanaka K, Perdomo J, Chong BH. Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes. PLoS One. 2014;9(4):e95253.

    Article  PubMed  PubMed Central  Google Scholar 

  • Charron F, Nemer M. GATA transcription factors and cardiac development. Semin Cell Dev Biol. 1999;10(1):85–91.

    Article  CAS  PubMed  Google Scholar 

  • Charron F, Paradis P, Bronchain O, Nemer G, Nemer M. Cooperative interaction between GATA-4 and GATA-6 regulates myocardial gene expression. Mol Cell Biol. 1999;19(6):4355–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charron F, Tsimiklis G, Arcand M, Robitaille L, Liang Q, Molkentin JD, Meloche S, Nemer M. Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA. Genes Dev. 2001;15(20):2702–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen B, Yates E, Huang Y, Kogut P, Ma L, Turner JR, Tao Y, Camoretti-Mercado B, Lang D, Svensson EC, Garcia JG, Gruber PJ, Morrisey EE, Solway J. Alternative promoter and GATA5 transcripts in mouse. Am J Physiol Gastrointest Liver Physiol. 2009;297(6):G1214–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Han ZQ, Yan WD, Tang CZ, Xie JY, Chen H, Hu DY. A novel mutation in GATA4 gene associated with dominant inherited familial atrial septal defect. J Thorac Cardiovasc Surg. 2010a;140(3):684–7.

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Mao J, Sun Y, Zhang Q, Cheng HB, Yan WH, Choy KW, Li H. A novel mutation of GATA4 in a familial atrial septal defect. Clin Chim Acta. 2010b;411(21–22):1741–5.

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Hsu R, Li Z, Kogut PC, Du Q, Rouser K, Camoretti-Mercado B, Solway J. Upstream stimulatory factor 1 activates GATA5 expression through an E-box motif. Biochem J. 2012;446(1):89–98.

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Moore TV, Li Z, Sperling AI, Zhang C, Andrade J, Rodriguez A, Bahroos N, Huang Y, Morrisey EE, Gruber PJ, Solway J. Gata5 deficiency causes airway constrictor hyperresponsiveness in mice. Am J Respir Cell Mol Biol. 2014;50(4):787–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Crispino JD, Lodish MB, Thurberg BL, Litovsky SH, Collins T, Molkentin JD, Orkin SH. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Genes Dev. 2001;15(7):839–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crossley M, Merika M, Orkin SH. Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains. Mol Cell Biol. 1995;15(5):2448–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai YS, Markham BE. p300 functions as a coactivator of transcription factor GATA-4. J Biol Chem. 2001;276(40):37178–85.

    Article  CAS  PubMed  Google Scholar 

  • Dai YS, Cserjesi P, Markham BE, Molkentin JD. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J Biol Chem. 2002;277(27):24390–8.

    Article  CAS  PubMed  Google Scholar 

  • Daoud G, Kempf H, Kumar D, Kozhemyakina E, Holowacz T, Kim DW, Ionescu A, Lassar AB. BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH. Development. 2014;141(20):3978–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deconinck AE, Mead PE, Tevosian SG, Crispino JD, Katz SG, Zon LI, Orkin SH. FOG acts as a repressor of red blood cell development in Xenopus. Development. 2000;127(10):2031–40.

    CAS  PubMed  Google Scholar 

  • Dodou E, Verzi MP, Anderson JP, Xu SM, Black BL. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development. 2004;131(16):3931–42.

    Article  CAS  PubMed  Google Scholar 

  • Durocher D, Charron F, Warren R, Schwartz RJ, Nemer M. The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors. EMBO J. 1997;16(18):5687–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans T. Regulation of cardiac gene expression by GATA-4/5/6. Trends Cardiovasc Med. 1997;7(3):75–83.

    Article  CAS  PubMed  Google Scholar 

  • Evans T, Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989;58(5):877–85.

    Article  CAS  PubMed  Google Scholar 

  • Fischer A, Klattig J, Kneitz B, Diez H, Maier M, Holtmann B, Englert C, Gessler M. Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts. Mol Cell Biol. 2005;25(20):8960–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujikura J, Yamato E, Yonemura S, Hosoda K, Masui S, Nakao K, Miyazaki Ji J, Niwa H. Differentiation of embryonic stem cells is induced by GATA factors. Genes Dev. 2002;16(7):784–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 2003;424(6947):443–7.

    Article  CAS  PubMed  Google Scholar 

  • Georges R, Nemer G, Morin M, Lefebvre C, Nemer M. Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol. 2008;28(12):4052–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu JY, Xu JH, Yu H, Yang YQ. Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation. Clinics (Sao Paulo). 2012;67(12):1393–9.

    Article  Google Scholar 

  • Heikinheimo M, Scandrett JM, Wilson DB. Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. Dev Biol. 1994;164(2):361–73.

    Article  CAS  PubMed  Google Scholar 

  • Hirayama-Yamada K, Kamisago M, Akimoto K, Aotsuka H, Nakamura Y, Tomita H, Furutani M, Imamura S, Takao A, Nakazawa M, Matsuoka R. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Am J Med Genet A. 2005;135(1):47–52.

    Article  PubMed  Google Scholar 

  • Huang WY, Cukerman E, Liew CC. Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding gene and isolation of a human GATA-4 cDNA. Gene. 1995;155(2):219–23.

    Article  CAS  PubMed  Google Scholar 

  • Huang RT, Xue S, Xu YJ, Yang YQ. Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot. Int J Mol Med. 2013;31(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  • Ip HS, Wilson DB, Heikinheimo M, Tang Z, Ting CN, Simon MC, Leiden JM, Parmacek MS. The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells. Mol Cell Biol. 1994;14(11):7517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ip HS, Wilson DB, Heikinheimo M, Leiden JM, Parmacek MS. The GATA-4 transcription factor transactivates the cardiac-specific troponin C promoter-enhancer in non-muscle cells. Adv Exp Med Biol. 1995;382:117–24.

    Article  CAS  PubMed  Google Scholar 

  • Jia Y, Takimoto K. GATA and FOG2 transcription factors differentially regulate the promoter for Kv4.2 K(+) channel gene in cardiac myocytes and PC12 cells. Cardiovasc Res. 2003;60(2):278–87.

    Article  CAS  PubMed  Google Scholar 

  • Kakita T, Hasegawa K, Morimoto T, Kaburagi S, Wada H, Sasayama S. p300 protein as a coactivator of GATA-5 in the transcription of cardiac-restricted atrial natriuretic factor gene. J Biol Chem. 1999;274(48):34096–102.

    Article  CAS  PubMed  Google Scholar 

  • Kassab K, Hariri H, Gharibeh L, Fahed AC, Zein M, El-Rassy I, Nemer M, El-Rassi I, Bitar F, Nemer G. GATA5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient. Mol Genet Genomic Med. 2016;4(2):160–71.

    Article  CAS  PubMed  Google Scholar 

  • Kelley C, Blumberg H, Zon LI, Evans T. GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development. 1993;118(3):817–27.

    CAS  PubMed  Google Scholar 

  • Kodo K, Yamagishi H. GATA transcription factors in congenital heart defects: a commentary on a novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet. 2010;55(10):637–8.

    Article  PubMed  Google Scholar 

  • Kodo K, Nishizawa T, Furutani M, Arai S, Yamamura E, Joo K, Takahashi T, Matsuoka R, Yamagishi H. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling. Proc Natl Acad Sci U S A. 2009;106(33):13933–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koutsourakis M, Langeveld A, Patient R, Beddington R, Grosveld F. The transcription factor GATA6 is essential for early extraembryonic development. Development. 1999;126(9):723–32.

    CAS  PubMed  Google Scholar 

  • Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, Soudais C, Leiden JM. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11(8):1048–60.

    Article  CAS  PubMed  Google Scholar 

  • Laforest B, Nemer M. GATA5 interacts with GATA4 and GATA6 in outflow tract development. Dev Biol. 2011;358(2):368–78.

    Article  CAS  PubMed  Google Scholar 

  • Laforest B, Andelfinger G, Nemer M. Loss of Gata5 in mice leads to bicuspid aortic valve. J Clin Invest. 2011;121(7):2876–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laverriere AC, MacNeill C, Mueller C, Poelmann RE, Burch JB, Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994;269(37):23177–84.

    CAS  PubMed  Google Scholar 

  • Lee Y, Shioi T, Kasahara H, Jobe SM, Wiese RJ, Markham BE, Izumo S. The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Biol. 1998;18(6):3120–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee KH, Evans S, Ruan TY, Lassar AB. SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer. Development. 2004;131(19):4709–23.

    Article  CAS  PubMed  Google Scholar 

  • Lepore JJ, Cappola TP, Mericko PA, Morrisey EE, Parmacek MS. GATA-6 regulates genes promoting synthetic functions in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2005;25(2):309–14.

    Article  CAS  PubMed  Google Scholar 

  • Lepore JJ, Mericko PA, Cheng L, Lu MM, Morrisey EE, Parmacek MS. GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J Clin Invest. 2006;116(4):929–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Liu WD, Yang ZL, Yuan F, Xu L, Li RG, Yang YQ. Prevalence and spectrum of GATA4 mutations associated with sporadic dilated cardiomyopathy. Gene. 2014;548(2):174–81.

    Article  CAS  PubMed  Google Scholar 

  • Liang Q, De Windt LJ, Witt SA, Kimball TR, Markham BE, Molkentin JD. The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J Biol Chem. 2001;276(32):30245–53.

    Article  CAS  PubMed  Google Scholar 

  • Lim JY, Kim WH, Kim J, Park SI. Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5. J Cell Biochem. 2008;103(1):182–94.

    Article  CAS  PubMed  Google Scholar 

  • Lin X, Huo Z, Liu X, Zhang Y, Li L, Zhao H, Yan B, Liu Y, Yang Y, Chen YH. A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet. 2010;55(10):662–7.

    Article  CAS  PubMed  Google Scholar 

  • Linhares VL, Almeida NA, Menezes DC, Elliott DA, Lai D, Beyer EC, Campos de Carvalho AC, Costa MW. Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovasc Res. 2004;64(3):402–11.

    Article  CAS  PubMed  Google Scholar 

  • Lou X, Deshwar AR, Crump JG, Scott IC. Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. Development. 2011;138(15):3113–23.

    Article  CAS  PubMed  Google Scholar 

  • Lourenco D, Brauner R, Rybczynska M, Nihoul-Fekete C, McElreavey K, Bashamboo A. Loss-of-function mutation in GATA4 causes anomalies of human testicular development. Proc Natl Acad Sci U S A. 2011;108(4):1597–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackay JP, Kowalski K, Fox AH, Czolij R, King GF, Crossley M. Involvement of the N-finger in the self-association of GATA-1. J Biol Chem. 1998;273(46):30560–7.

    Article  CAS  PubMed  Google Scholar 

  • Maitra M, Schluterman MK, Nichols HA, Richardson JA, Lo CW, Srivastava D, Garg V. Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development. Dev Biol. 2009;326(2):368–77.

    Article  CAS  PubMed  Google Scholar 

  • Maitra M, Koenig SN, Srivastava D, Garg V. Identification of GATA6 sequence variants in patients with congenital heart defects. Pediatr Res. 2010;68(4):281–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin DI, Orkin SH. Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev. 1990;4(11):1886–98.

    Article  CAS  PubMed  Google Scholar 

  • McBride K, Charron F, Lefebvre C, Nemer M. Interaction with GATA transcription factors provides a mechanism for cell-specific effects of c-Fos. Oncogene. 2003;22(52):8403–12.

    Article  CAS  PubMed  Google Scholar 

  • Messaoudi S, He Y, Gutsol A, Wight A, Hebert RL, Vilmundarson RO, Makrigiannis AP, Chalmers J, Hamet P, Tremblay J, McPherson R, Stewart AF, Touyz RM, Nemer M. Endothelial Gata5 transcription factor regulates blood pressure. Nat Commun. 2015;6:8835.

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto S, Kawamura T, Morimoto T, Ono K, Wada H, Kawase Y, Matsumori A, Nishio R, Kita T, Hasegawa K. Histone acetyltransferase activity of p300 is required for the promotion of left ventricular remodeling after myocardial infarction in adult mice in vivo. Circulation. 2006;113(5):679–90.

    Article  CAS  PubMed  Google Scholar 

  • Molkentin JD. The zinc finger-containing transcription factors GATA-4, −5, and −6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem. 2000;275(50):38949–52.

    Article  CAS  PubMed  Google Scholar 

  • Molkentin JD, Lin Q, Duncan SA, Olson EN. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 1997;11(8):1061–72.

    Article  CAS  PubMed  Google Scholar 

  • Morin S, Charron F, Robitaille L, Nemer M. GATA-dependent recruitment of MEF2 proteins to target promoters. EMBO J. 2000;19(9):2046–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morin S, Paradis P, Aries A, Nemer M. Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor. Mol Cell Biol. 2001;21(4):1036–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrisey EE, Ip HS, Lu MM, Parmacek MS. GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Dev Biol. 1996;177(1):309–22.

    Article  CAS  PubMed  Google Scholar 

  • Morrisey EE, Ip HS, Tang Z, Lu MM, Parmacek MS. GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. Dev Biol. 1997a;183(1):21–36.

    Article  CAS  PubMed  Google Scholar 

  • Morrisey EE, Ip HS, Tang Z, Parmacek MS. GATA-4 activates transcription via two novel domains that are conserved within the GATA-4/5/6 subfamily. J Biol Chem. 1997b;272(13):8515–24.

    Article  CAS  PubMed  Google Scholar 

  • Morrisey EE, Tang Z, Sigrist K, Lu MM, Jiang F, Ip HS, Parmacek MS. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev. 1998;12(22):3579–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moskowitz IP, Kim JB, Moore ML, Wolf CM, Peterson MA, Shendure J, Nobrega MA, Yokota Y, Berul C, Izumo S, Seidman JG, Seidman CE. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007;129(7):1365–76.

    Article  CAS  PubMed  Google Scholar 

  • Murakami A, Ishida S, Dickson C. GATA-4 interacts distinctively with negative and positive regulatory elements in the Fgf-3 promoter. Nucleic Acids Res. 2002;30(4):1056–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadeau M, Georges RO, Laforest B, Yamak A, Lefebvre C, Beauregard J, Paradis P, Bruneau BG, Andelfinger G, Nemer M. An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci U S A. 2010;107(45):19356–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nemer G, Nemer M. Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells. Development. 2002;129(17):4045–55.

    CAS  PubMed  Google Scholar 

  • Nemer G, Nemer M. Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol. 2003;254(1):131–48.

    Article  CAS  PubMed  Google Scholar 

  • Newton A, Mackay J, Crossley M. The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds GATC motifs in DNA. J Biol Chem. 2001;276(38):35794–801.

    Article  CAS  PubMed  Google Scholar 

  • Nishida W, Nakamura M, Mori S, Takahashi M, Ohkawa Y, Tadokoro S, Yoshida K, Hiwada K, Hayashi K, Sobue K. A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes. J Biol Chem. 2002;277(9):7308–17.

    Article  CAS  PubMed  Google Scholar 

  • Oka T, Dai YS, Molkentin JD. Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo. Mol Cell Biol. 2005;25(15):6649–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oka T, Maillet M, Watt AJ, Schwartz RJ, Aronow BJ, Duncan SA, Molkentin JD. Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ Res. 2006;98(6):837–45.

    Article  CAS  PubMed  Google Scholar 

  • Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Trainor C, Appella E, Stahl SJ, Gronenborn AM. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science. 1993;261(5120):438–46.

    Article  CAS  PubMed  Google Scholar 

  • Padang R, Bagnall RD, Richmond DR, Bannon PG, Semsarian C. Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease. J Mol Cell Cardiol. 2012;53(2):277–81.

    Article  CAS  PubMed  Google Scholar 

  • Pedone PV, Omichinski JG, Nony P, Trainor C, Gronenborn AM, Clore GM, Felsenfeld G. The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains. EMBO J. 1997;16(10):2874–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pehlivan T, Pober BR, Brueckner M, Garrett S, Slaugh R, Van Rheeden R, Wilson DB, Watson MS, Hing AV. GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease. Am J Med Genet. 1999;83(3):201–6.

    Article  CAS  PubMed  Google Scholar 

  • Peng T, Wang L, Zhou SF, Li X. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica. 2010;138(11–12):1231–40.

    Article  CAS  PubMed  Google Scholar 

  • Perdomo J, Jiang XM, Carter DR, Khachigian LM, Chong BH. SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4. PLoS One. 2012;7(11):e50637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlman H, Suzuki E, Simonson M, Smith RC, Walsh K. GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest. J Biol Chem. 1998;273(22):13713–8.

    Article  CAS  PubMed  Google Scholar 

  • Plageman TF Jr, Yutzey KE. Differential expression and function of Tbx5 and Tbx20 in cardiac development. J Biol Chem. 2004;279(18):19026–34.

    Article  CAS  PubMed  Google Scholar 

  • Pu WT, Ishiwata T, Juraszek AL, Ma Q, Izumo S. GATA4 is a dosage-sensitive regulator of cardiac morphogenesis. Dev Biol. 2004;275(1):235–44.

    Article  CAS  PubMed  Google Scholar 

  • Rajagopal SK, Ma Q, Obler D, Shen J, Manichaikul A, Tomita-Mitchell A, Boardman K, Briggs C, Garg V, Srivastava D, Goldmuntz E, Broman KW, Benson DW, Smoot LB, Pu WT. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 2007;43(6):677–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rawnsley DR, Xiao J, Lee JS, Liu X, Mericko-Ishizuka P, Kumar V, He J, Basu A, Lu M, Lynn FC, Pack M, Gasa R, Kahn ML. The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. J Biol Chem. 2013;288(34):24429–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reiter JF, Alexander J, Rodaway A, Yelon D, Patient R, Holder N, Stainier DY. Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 1999;13(22):2983–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivera-Feliciano J, Lee KH, Kong SW, Rajagopal S, Ma Q, Springer Z, Izumo S, Tabin CJ, Pu WT. Development of heart valves requires Gata4 expression in endothelial-derived cells. Development. 2006;133(18):3607–18.

    Article  CAS  PubMed  Google Scholar 

  • Robert NM, Miyamoto Y, Taniguchi H, Viger RS. LRH-1/NR5A2 cooperates with GATA factors to regulate inhibin alpha-subunit promoter activity. Mol Cell Endocrinol. 2006;257–258:65–74.

    Article  PubMed  CAS  Google Scholar 

  • Rong L, Liu J, Qi Y, Graham AM, Parmacek MS, Li S. GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation. Mol Biol Cell. 2012;23(18):3754–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Rooij E, Doevendans PA, de Theije CC, Babiker FA, Molkentin JD, de Windt LJ. Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy. J Biol Chem. 2002;277(50):48617–26.

    Article  PubMed  Google Scholar 

  • Schlange T, Andree B, Arnold HH, Brand T. BMP2 is required for early heart development during a distinct time period. Mech Dev. 2000;91(1–2):259–70.

    Article  CAS  PubMed  Google Scholar 

  • Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science. 1998;281(5373):108–11.

    Article  CAS  PubMed  Google Scholar 

  • Sepulveda JL, Belaguli N, Nigam V, Chen CY, Nemer M, Schwartz RJ. GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating early cardiac gene expression. Mol Cell Biol. 1998;18(6):3405–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sepulveda JL, Vlahopoulos S, Iyer D, Belaguli N, Schwartz RJ. Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity. J Biol Chem. 2002;277(28):25775–82.

    Article  CAS  PubMed  Google Scholar 

  • Shi LM, Tao JW, Qiu XB, Wang J, Yuan F, Xu L, Liu H, Li RG, Xu YJ, Wang Q, Zheng HZ, Li X, Wang XZ, Zhang M, Qu XK, Yang YQ. GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. Int J Mol Med. 2014;33(5):1219–26.

    Article  CAS  PubMed  Google Scholar 

  • Shirvani S, Xiang F, Koibuchi N, Chin MT. CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6. Biochem Biophys Res Commun. 2006;339(1):151–6.

    Article  CAS  PubMed  Google Scholar 

  • Silverman E, Yivgi-Ohana N, Sher N, Bell M, Eimerl S, Orly J. Transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene: GATA-4 and CCAAT/enhancer-binding protein beta confer synergistic responsiveness in hormone-treated rat granulosa and HEK293 cell models. Mol Cell Endocrinol. 2006;252(1–2):92–101.

    Article  CAS  PubMed  Google Scholar 

  • Smagulova FO, Manuylov NL, Leach LL, Tevosian SG. GATA4/FOG2 transcriptional complex regulates Lhx9 gene expression in murine heart development. BMC Dev Biol. 2008;8:67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sommer H, Beltran JP, Huijser P, Pape H, Lonnig WE, Saedler H, Schwarz-Sommer Z. Deficiens, a homeotic gene involved in the control of flower morphogenesis in Antirrhinum majus: the protein shows homology to transcription factors. EMBO J. 1990;9(3):605–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997;16(2):154–60.

    Article  CAS  PubMed  Google Scholar 

  • Stennard FA, Costa MW, Elliott DA, Rankin S, Haast SJ, Lai D, McDonald LP, Niederreither K, Dolle P, Bruneau BG, Zorn AM, Harvey RP. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol. 2003;262(2):206–24.

    Article  CAS  PubMed  Google Scholar 

  • Sun Q, Chen G, Streb JW, Long X, Yang Y, Stoeckert CJ Jr, Miano JM. Defining the mammalian CArGome. Genome Res. 2006;16(2):197–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. 1996;38(3):283–90.

    Article  CAS  PubMed  Google Scholar 

  • Svensson EC, Tufts RL, Polk CE, Leiden JM. Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes. Proc Natl Acad Sci U S A. 1999;96(3):956–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takaya T, Kawamura T, Morimoto T, Ono K, Kita T, Shimatsu A, Hasegawa K. Identification of p300-targeted acetylated residues in GATA4 during hypertrophic responses in cardiac myocytes. J Biol Chem. 2008;283(15):9828–35.

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126(6):1269–80.

    CAS  PubMed  Google Scholar 

  • Terada R, Warren S, Lu JT, Chien KR, Wessels A, Kasahara H. Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 2011;91(2):289–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tevosian SG, Deconinck AE, Cantor AB, Rieff HI, Fujiwara Y, Corfas G, Orkin SH. FOG-2: a novel GATA-family cofactor related to multitype zinc-finger proteins friend of GATA-1 and U-shaped. Proc Natl Acad Sci U S A. 1999;96(3):950–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet. 2007;44(12):779–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trainor CD, Omichinski JG, Vandergon TL, Gronenborn AM, Clore GM, Felsenfeld G. A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction. Mol Cell Biol. 1996;16(5):2238–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trainor CD, Ghirlando R, Simpson MA. GATA zinc finger interactions modulate DNA binding and transactivation. J Biol Chem. 2000;275(36):28157–66.

    CAS  PubMed  Google Scholar 

  • Trinh LA, Yelon D, Stainier DY. Hand2 regulates epithelial formation during myocardial diferentiation. Curr Biol. 2005;15(5):441–6.

    Article  PubMed  CAS  Google Scholar 

  • Tsai SF, Strauss E, Orkin SH. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev. 1991;5(6):919–31.

    Article  CAS  PubMed  Google Scholar 

  • Visvader JE, Crossley M, Hill J, Orkin SH, Adams JM. The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. Mol Cell Biol. 1995;15(2):634–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wada H, Hasegawa K, Morimoto T, Kakita T, Yanazume T, Abe M, Sasayama S. Calcineurin-GATA-6 pathway is involved in smooth muscle-specific transcription. J Cell Biol. 2002;156(6):983–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Morishima M, Zheng M, Uchino T, Mannen K, Takahashi A, Nakaya Y, Komuro I, Ono K. Transcription factors Csx/Nkx2.5 and GATA4 distinctly regulate expression of Ca2+ channels in neonatal rat heart. J Mol Cell Cardiol. 2007;42(6):1045–53.

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Fang M, Liu XY, Xin YF, Liu ZM, Chen XZ, Wang XZ, Fang WY, Liu X, Yang YQ. A novel GATA4 mutation responsible for congenital ventricular septal defects. Int J Mol Med. 2011;28(4):557–64.

    CAS  PubMed  Google Scholar 

  • Wang XH, Huang CX, Wang Q, Li RG, Xu YJ, Liu X, Fang WY, Yang YQ. A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. Int J Mol Med. 2013;31(1):43–50.

    Article  PubMed  CAS  Google Scholar 

  • Warren CM, Tanaka JW, Holroyd CB. What can topology changes in the oddball N2 reveal about underlying processes? Neuroreport. 2011;22(17):870–4.

    Article  PubMed  Google Scholar 

  • Watt AJ, Battle MA, Li J, Duncan SA. GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci U S A. 2004;101(34):12573–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei D, Bao H, Liu XY, Zhou N, Wang Q, Li RG, Xu YJ, Yang YQ. GATA5 loss-of-function mutations underlie tetralogy of fallot. Int J Med Sci. 2013a;10(1):34–42.

    Article  CAS  PubMed  Google Scholar 

  • Wei D, Bao H, Zhou N, Zheng GF, Liu XY, Yang YQ. GATA5 loss-of-function mutation responsible for the congenital ventriculoseptal defect. Pediatr Cardiol. 2013b;34(3):504–11.

    Article  PubMed  Google Scholar 

  • Yang YQ, Li L, Wang J, Liu XY, Chen XZ, Zhang W, Wang XZ, Jiang JQ, Liu X, Fang WY. A novel GATA4 loss-of-function mutation associated with congenital ventricular septal defect. Pediatr Cardiol. 2012a;33(4):539–46.

    Article  PubMed  Google Scholar 

  • Yang YQ, Wang J, Wang XH, Wang Q, Tan HW, Zhang M, Shen FF, Jiang JQ, Fang WY, Liu X. Mutational spectrum of the GATA5 gene associated with familial atrial fibrillation. Int J Cardiol. 2012b;157(2):305–7.

    Article  CAS  PubMed  Google Scholar 

  • Yang YQ, Gharibeh L, Li RG, Xin YF, Wang J, Liu ZM, Qiu XB, Xu YJ, Xu L, Qu XK, Liu X, Fang WY, Huang RT, Xue S, Nemer G. GATA4 loss-of-function mutations underlie familial tetralogy of fallot. Hum Mutat. 2013;34(12):1662–71.

    Article  CAS  PubMed  Google Scholar 

  • Zeisberg EM, Ma Q, Juraszek AL, Moses K, Schwartz RJ, Izumo S, Pu WT. Morphogenesis of the right ventricle requires myocardial expression of Gata4. J Clin Invest. 2005;115(6):1522–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Li X, Shen A, Jiao W, Guan X, Li Z. GATA4 mutations in 486 Chinese patients with congenital heart disease. Eur J Med Genet. 2008;51(6):527–35.

    Article  PubMed  Google Scholar 

  • Zhang XL, Dai N, Tang K, Chen YQ, Chen W, Wang J, Zhao CM, Yuan F, Qiu XB, Qu XK, Yang YQ, Xu YW. GATA5 loss-of-function mutation in familial dilated cardiomyopathy. Int J Mol Med. 2015;35(3):763–70.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The author thanks Dr. Julian Solway for helpful discussion and comments. The author thanks all investigators who have contributed to our understanding of the role of GATA transcriptional factors in the heart development and cardiovascular disease.

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  1. Department of Medicine, University of Chicago, Chicago, IL, USA

    Bohao Chen

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  1. Zhongshan Hospital, Fudan University, Shanghai, China

    Hong Jiang

  2. Zhongshan Hospital, Fudan University, Shanghai, China

    Ming Liu

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Chen, B. (2018). GATA Transcription Factors and Cardiovascular Disease. In: Jiang, H., Liu, M. (eds) Heart Genomics. Translational Bioinformatics, vol 16. Springer, Singapore. https://doi.org/10.1007/978-981-13-1429-2_5

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