The Chicken GATA-6 Locus Contains Multiple Control Regions That Confer Distinct Patterns of Heart Region-specific Expression in Transgenic Mouse Embryos*
Abstract
The GATA-6 transcription factor is expressed in cardiogenic cells and during subsequent stages of heart development in diverse vertebrate species. To gain insights into the molecular events that govern this heart-restricted expression, we isolated the chickenGATA-6 gene and used several approaches to screen for associated control regions. Our analysis of two chickenGATA-6/lacZ constructs in transgenic mouse embryos was particularly revealing. One GATA-6/lacZ construct, which has 1.5 kilobase pairs of upstream sequences along with the promoter and first intron, was expressed exclusively in the atrioventricular canal region of the heart. This expression pattern is novel and appears to mark specialized myocardial cells that induce underlying endocardial cells to initiate valve formation. The other GATA-6/lacZconstruct, which has an additional 7.7 kilobase pairs of upstream sequences, was expressed in the ventricle and outflow tract in addition to the atrioventricular canal. The failure of these GATA-6control regions to function as enhancers in transfected cardiac myocyte cultures underscores the importance of using transgenic approaches to elucidate transcriptional controls that function in the developing heart. Although the endogenous GATA-6 gene is expressed throughout the heart, our results indicate that this is effected in a heart region-specific manner.
Footnotes
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↵* This work was supported by National Institutes of Health Grants GM35535 and HL55373 (to J. B. E. B.) and CA-06927 (to the Fox Chase Cancer Center) and by the Commonwealth of Pennsylvania.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Inst. for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Tel.: 215-728-3696; Fax: 215-728-3574; E-mail:jb_burch{at}fccc.edu.
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↵1 The abbreviations used are: AV, atrioventricular; 5′-RACE, rapid amplification of 5′-cDNA ends; CAT, chloramphenicol acetyltransferase; kb, kilobase pair(s); bp, base pair(s); FBS, fetal bovine serum; HS, hypersensitive.
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↵2 C. MacNeill and J. B. E. Burch, unpublished result.
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- Received June 17, 1997.
- Revision received July 30, 1997.
