GATA-4 activates transcription via two novel domains that are conserved within the GATA-4/5/6 subfamily.
GATA-4 is one of the earliest developmental markers of the precardiac mesoderm, heart, and gut and has been shown to activate regulatory elements controlling transcription of genes encoding cardiac-specific proteins. To elucidate the molecular mechanisms underlying the transcriptional activity of the GATA-4 protein, structure-function analyses were performed. These analyses revealed that the C-terminal zinc finger and adjacent basic domain of GATA-4 is bifunctional, modulating both DNA-binding and nuclear localization activities. The N terminus of the protein encodes two independent transcriptional Activation Domains (amino acids 1-74 and amino acids 130-177). Amino acid residues were identified within each domain that are required for transcriptional activation. Finally, we have shown that regions of Xenopus GATA-5 and -6 corresponding to Activation Domains I and II, respectively, function as potent transcriptional activators. The identification and functional characterization of two evolutionarily conserved transcriptional Activation Domains within the GATA-4/5/6 subfamily suggests that each of these domains modulates critical functions in the transcriptional regulatory program(s) encoded by GATA-4, -5, and -6 during vertebrate development. As such these data provide novel insights into the molecular mechanisms that control development of the heart.
Morrisey
E E
EE
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Ip
H S
HS
Tang
Z
Z
Parmacek
M S
MS
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D050991:GATA4 Transcription Factor; D050992:GATA5 Transcription Factor; D050993:GATA6 Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D019209:Troponin C / Q000235:genetics; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D050992:GATA5 Transcription Factor; D050993:GATA6 Transcription Factor; C494756:Gata5 protein, mouse; D014157:Transcription Factors; D019209:Troponin C; D004247:DNA