title: Transcriptional regulation of the cardiac-specific MLC2 gene during Xenopus embryonic development.
abstract: The mechanisms by which transcription factors, which are not themselves tissue restricted, establish cardiomyocyte-specific patterns of transcription in vivo are unknown. Nor do we understand how positional cues are integrated to provide regionally distinct domains of gene expression within the developing heart. We describe regulation of the Xenopus XMLC2 gene, which encodes a regulatory myosin light chain of the contractile apparatus in cardiac muscle. This gene is expressed from the onset of cardiac differentiation in the frog embryo and is expressed throughout all the myocardium, both before and after heart chamber formation. Using transgenesis in frog embryos, we have identified an 82 bp enhancer within the proximal promoter region of the gene that is necessary and sufficient for heart-specific expression of an XMLC2 transgene. This enhancer is composed of two GATA sites and a composite YY1/CArG-like site. We show that the low-affinity SRF site is essential for transgene expression and that cardiac-specific expression also requires the presence of at least one adjacent GATA site. The overlapping YY1 site within the enhancer appears to act primarily as a repressor of ectopic expression, although it may also have a positive role. Finally, we show that the frog MLC2 promoter drives pan myocardial expression of a transgene in mice, despite the more restricted patterns of expression of murine MLC2 genes. We speculate that a common regulatory mechanism may be responsible for pan-myocardial expression of XMLC2 in both the frog and mouse, modulation of which could have given rise to more restricted patterns of expression within the heart of higher vertebrates.
authors.affiliation: Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Branko V
authors.initials: BV
authors.lastname: Latinkic
authors.forename: Brian
authors.initials: B
authors.lastname: Cooper
authors.forename: Stuart
authors.initials: S
authors.lastname: Smith
authors.forename: Surendra
authors.initials: S
authors.lastname: Kotecha
authors.forename: Norma
authors.initials: N
authors.lastname: Towers
authors.forename: Duncan
authors.initials: D
authors.lastname: Sparrow
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D024722:Cardiac Myosins / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology* / Q000502:physiology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D018994:Myosin Light Chains / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014981:Xenopus
chemical_list: D004268:DNA-Binding Proteins; D018994:Myosin Light Chains; C107184:myosin light chain 2; D004247:DNA; D024722:Cardiac Myosins