title: The deoxyribonucleic acid regions involved in the hormonal regulation of thyroglobulin gene expression.
abstract: Transcription of the thyroglobulin (TG) gene is stimulated by TSH via cAMP. We have characterized the sequence elements responsible for the hormone-dependent expression of TG gene in rat thyroid FRTL-5 cells using internal deletion and linker-scanning mutants of the minimal TG promoter (-170 basepairs) fused with the bacterial chloramphenicol acetyltransferase reporter gene. The TG gene is regulated by at least two regions located between -165 and -140 bp (TG-III) and between -95 and -65 bp (TG-I) from the transcription initiation site. The intervening region can be deleted without significant effect on the promoter activity. Either of the two regions alone does not promote hormone-dependent transcription. A DNase footprinting assay showed that TG-I and TG-III are the principal protein-binding sites and that the proteins interacting with these two regions are induced by TSH or cAMP. These results suggest that the hormone-dependent expression of TG gene may be achieved by cooperative interaction of the proteins bound to TG-I and TG-III.
authors.affiliation: Department of Biochemistry, University of North Carolina, Chapel Hill 27599-7260.
authors.forename: N T
authors.initials: NT
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Kamikubo
authors.forename: K J
authors.initials: KJ
authors.lastname: Chai
authors.forename: L R
authors.initials: LR
authors.lastname: Kao
authors.forename: A J
authors.initials: AJ
authors.lastname: Sinclair
authors.forename: S N
authors.initials: SN
authors.lastname: Nayfeh
authors.forename: C B
authors.initials: CB
authors.lastname: Chae
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002872:Chromosome Deletion; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland; D013972:Thyrotropin / Q000494:pharmacology*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D015345:Oligonucleotide Probes; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D000242:Cyclic AMP