Endocrinology, Vol 128, 111-118, Copyright © 1991 by Endocrine Society

ARTICLES

The deoxyribonucleic acid regions involved in the hormonal regulation of thyroglobulin gene expression

NT Lee, K Kamikubo, KJ Chai, LR Kao, AJ Sinclair, SN Nayfeh and CB Chae
Department of Biochemistry, University of North Carolina, Chapel Hill 27599-7260.

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.

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