Identification of a thyroid-specific and cAMP-responsive enhancer in the upstream sequences of the human thyroglobulin promoter.
Functional analysis of remote 5'-flanking sequences from the human thyroglobulin gene in primary cultured dog thyrocytes led to the identification of a partly cAMP-responsive enhancer, located between -3.6 to -2.2 kb from the transcriptional start site. Deletion analysis of the 1.4 kb-long region localised the enhancer activity in a 0.5 kb-long fragment (located between -3.2 and -2.7 kb relative to transcription start), which could be divided into two functional sub-fragments of 0.2 and 0.3 kb. A potential binding site for the CREB/ATF transcription factors was found in the 0.3 kb element. The complete enhancer region had no detectable activity when assayed in Hela cells, suggesting that it constituted a thyroid-specific regulatory element. Accordingly, footprinting experiments revealed the presence of several binding sites for Thyroid Transcription Factor-1 (TTF-1) in both the 0.2 and 0.3 kb elements.
Berg
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V
IRIBHN, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Vassart
G
G
Christophe
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D
D001483:Base Sequence; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D013937:Thymidine Kinase / Q000235:genetics; D013954:Thyroglobulin / Q000235:genetics* / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013954:Thyroglobulin; D000242:Cyclic AMP; D013937:Thymidine Kinase