title: Divergent transcriptional enhancer factor-1 regulates the cardiac troponin T promoter.
abstract: MCAT elements are essential for cardiac gene expression during development. Avian transcriptional enhancer factor-1 (TEF-1) proteins are muscle-enriched and contribute to MCAT binding activities. However, direct activation of MCAT-driven promoters by TEF-1-related proteins has not been uniformly achieved. Divergent TEF (DTEF)-1 is a unique member of the TEF-1 multigene family with abundant transcripts in the heart but not in skeletal muscle. Herein we show that DTEF-1 proteins are highly expressed in the heart. Protein expression is activated at very early stages of chick embryogenesis (Hamburger-Hamilton stage 4, 16-18 h), after which DTEF-1 becomes abundant in the sinus venosus and is expressed in the trabeculated ventricular myocardium and ventricular outflow tracts. By chromatin immunoprecipitation, DTEF-1 interacts with the cardiac troponin T (cTnT) promoter in vivo. DTEF-1 also interacts with MEF- 2 by coimmunoprecipitation and independently or cooperatively (with MEF-2) trans-activates the cTnT promoter. DTEF-1 isoforms do not activate the cTnT promoter in fibroblasts or skeletal muscle. DTEF-1 expression occurs very early in chick embryogenesis (16-18 h), preceding sarcomeric protein expression, and it activates cardiac promoters. As such, DTEF-1 may be an early marker of the myocardial phenotype. DTEF-1 trans-activates the cTnT promoter in a tissue-specific fashion independent of AT-rich, MEF-2, or GATA sites. The observed spatial pattern suggests decreasing levels of expression from the cardiac inlet to the ventricular outflow tracts, which may mark a cardiogenic or differentiation pathway that parallels the direction of flow through the developing chick heart.
authors.affiliation: Department of Surgery, Univ. of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Azakie
authors.forename: Lauren
authors.initials: L
authors.lastname: Lamont
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Fineman
authors.forename: Youping
authors.initials: Y
authors.lastname: He
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020107:Troponin T / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C098771:DTEF-1 protein, Gallus gallus; D018006:Myogenic Regulatory Factors; D020033:Protein Isoforms; D014157:Transcription Factors; D020107:Troponin T