title: An Nkx-dependent enhancer regulates cGATA-6 gene expression during early stages of heart development.
abstract: The evolutionarily conserved GATA-6 transcription factor is an early and persistent marker of heart development in diverse vertebrate species. We previously found evidence for a functionally conserved heart-specific enhancer upstream of the chicken GATA-6 (cGATA-6) gene and in the present study we used transgenic mouse assays to further characterize this regulatory module. We show that this enhancer is activated in committed precursor cells within the cardiac crescent and that it remains active in essentially all cardiogenic cells through the linear heart stage. Although this enhancer can account for cGATA-6 gene expression early in the cardiogenic program, it is not able to maintain expression throughout the heart later in development. In particular, the enhancer is sequentially downregulated along the posterior to anterior axis, with activity becoming confined to outflow tract myocardium. Enhancers with similar properties have been shown to regulate the early heart-restricted expression of the mouse Nkx2.5 transcription factor gene. Whereas these Nkx2.5 enhancers are GATA-dependent, we show that the cGATA-6 enhancer is Nkx-dependent. We speculate that these enhancers are silenced to allow GATA-6 and Nkx2.5 gene expression to be governed by region-specific enhancers in the multichambered heart.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Davis
authors.forename: A
authors.initials: A
authors.lastname: Wessels
authors.forename: J B
authors.initials: JB
authors.lastname: Burch
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D050993:GATA6 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins
chemical_list: D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D029867:Xenopus Proteins