The Zinc Finger-containing Transcription Factors GATA-4, -5, and -6

Abstract

myocyte enhancer factor-2 thyroid transcription factor-1 nuclear factor of activated T-cells-c4 friend of GATA-2 CREB-binding protein Six GATA transcription factors have been identified in vertebrates, each of which contains a highly conserved DNA binding domain consisting of two zinc fingers of the motif Cys-X2-Cys-X17-Cys-X2-Cys (1Evans T. Felsenfeld G. Cell. 1989; 58: 877-885Abstract Full Text PDF PubMed Scopus (450) Google Scholar, 2Tsai S.-F. Martin D.I. Zon L.I. D'Andrea A.D. Wong G.G. Orkin S.H. Nature. 1989; 339: 446-451Crossref PubMed Scopus (663) Google Scholar, 3Yamamoto M. Ko L.J. Leonard M.W. Beug H. Orkin S.H. Engel J.D. Genes Dev. 1990; 4: 1650-1662Crossref PubMed Scopus (451) Google Scholar, 4Arceci R.J. King A.A.J. Simon M.C. Orkin S.H. Wilson D.B. Mol. Cell. Biol. 1993; 13: 2235-2246Crossref PubMed Google Scholar, 5Kelley C. Blumberg H. Zon L.I. Evans T. Development. 1993; 118: 817-827Crossref PubMed Google Scholar, 6Laverriere A.C. MacNeill C. Mueller C. Poelmann R.E. Burch J.B.E. Evans T. J. Biol. Chem. 1994; 269: 23177-23184Abstract Full Text PDF PubMed Google Scholar, 7Morrisey E.E. Ip H.S. Lu M.M. Parmacek M.S. Dev. Biol. 1996; 177: 309-322Crossref PubMed Scopus (382) Google Scholar, 8Morrisey E.E. Ip H.S. Tang Z. Lu M.M. Parmacek M.S. Dev. Biol. 1997; 183: 21-36Crossref PubMed Scopus (213) Google Scholar, 9Suzuki E. Evans T. Lowry J. Truong L. Bell D.W. Testa J.R. Walsh K. Genomics. 1996; 38: 283-290Crossref PubMed Scopus (117) Google Scholar) that directs binding to the nucleotide sequence element (A/T)GATA(A/G) (10Ko J.L. Engel J.D. Mol. Cell. Biol. 1993; 13: 4011-4022Crossref PubMed Scopus (505) Google Scholar, 11Merika M. Orkin S.H. Mol. Cell. Biol. 1993; 13: 3999-4010Crossref PubMed Scopus (560) Google Scholar). Based on their expression patterns, the GATA proteins have been divided into two subfamilies, GATA-1, -2, and -3 and GATA-4, -5, and -6. GATA-1, -2, and -3 genes are prominently expressed in hematopoietic stem cells where they regulate differentiation-specific gene expression in T-lymphocytes, erythroid cells, and megakaryocytes (reviewed in Ref. 12Orkin S.H. Int. J. Dev. Biol. 1998; 42: 927-934PubMed Google Scholar). GATA-4, -5, and -6 genes are expressed in various mesoderm- and endoderm-derived tissues such as heart, liver, lung, gonad, and gut where they play critical roles in regulating tissue-specific gene expression (4Arceci R.J. King A.A.J. Simon M.C. Orkin S.H. Wilson D.B. Mol. Cell. Biol. 1993; 13: 2235-2246Crossref PubMed Google Scholar, 5Kelley C. Blumberg H. Zon L.I. Evans T. Development. 1993; 118: 817-827Crossref PubMed Google Scholar, 6Laverriere A.C. MacNeill C. Mueller C. Poelmann R.E. Burch J.B.E. Evans T. J. Biol. Chem. 1994; 269: 23177-23184Abstract Full Text PDF PubMed Google Scholar, 7Morrisey E.E. Ip H.S. Lu M.M. Parmacek M.S. Dev. Biol. 1996; 177: 309-322Crossref PubMed Scopus (382) Google Scholar, 8Morrisey E.E. Ip H.S. Tang Z. Lu M.M. Parmacek M.S. Dev. Biol. 1997; 183: 21-36Crossref PubMed Scopus (213) Google Scholar, 9Suzuki E. Evans T. Lowry J. Truong L. Bell D.W. Testa J.R. Walsh K. Genomics. 1996; 38: 283-290Crossref PubMed Scopus (117) Google Scholar). Consistent with the observed expression patterns for GATA-4, -5, and -6, targeted disruption of each gene in the mouse has revealed important functions in heart, endoderm, lung epithelium, and genitourinary tract formation. Here we will discuss the biochemical characteristics and transcriptional regulatory roles of GATA-4, -5, and -6 transcription factors. The mouse GATA-4, -5, and -6 genes encode proteins of 48, 42, and 45 kDa, respectively (4Arceci R.J. King A.A.J. Simon M.C. Orkin S.H. Wilson D.B. Mol. Cell. Biol. 1993; 13: 2235-2246Crossref PubMed Google Scholar, 7Morrisey E.E. Ip H.S. Lu M.M. Parmacek M.S. Dev. Biol. 1996; 177: 309-322Crossref PubMed Scopus (382) Google Scholar, 8Morrisey E.E. Ip H.S. Tang Z. Lu M.M. Parmacek M.S. Dev. Biol. 1997; 183: 21-36Crossref PubMed Scopus (213) Google Scholar). Each protein contains a highly conserved DNA binding domain that consists of two zinc finger motifs and two adjacent stretches of basic amino acids (Fig. 1, A and B).GATA-4, -5, and -6 are ∼85% identical to one another at the amino acid level within the DNA binding region containing the zinc finger and basic regions (Fig. 1 B). Furthermore, mouse GATA-4 is ∼70% identical to mouseGATA-1 and Drosophila pannier within the DNA binding region, suggesting a high degree of sequence conservation between divergent GATA family members and across evolutionary disparate organisms (Fig. 1 A). Given the high degree of sequence identity between GATA protein family members, predictions can be drawn as to the residues that mediate DNA binding in GATA-4, -5, and -6 based on structural and mutagenesis studies performed in GATA-1. A number of reports have demonstrated that only the C-terminal zinc finger and adjacent basic domain are necessary for specific DNA binding in vitro (13Omichinski J.G. Trainor C.