Induction of nuclear protein factors specific for hormone-responsive region during activation of thyroglobulin gene by thyrotropin in rat thyroid FRTL-5 cells.
We have investigated the mechanism of stimulation of thyroglobulin gene expression by thyrotropin (TSH) and cAMP in rat thyroid FRTL-5 cells. In contrast to the c-fos gene, induction of the thyroglobulin gene by TSH or cAMP is slow (10 h) and sensitive to cycloheximide treatment. We have identified a TSH and cAMP-responsive region of thyroglobulin gene between - 171 and - 140 base pairs from the transcription initiation site. The hormone-responsive region contains DNA sequence elements similar to the consensus cAMP-responsive element as well as the transcription factor AP-1-binding site but with opposite sequence polarity. Three DNA-protein complexes are formed when the hormone-responsive region is incubated with nuclear extracts of FRTL-5 cells. Formation of these complexes is dependent on TSH or cAMP stimulation, thus suggesting that the factors involved in binding to the hormone-responsive region may be induced by TSH. Although the identity of these factors is not yet known, they do not appear to be related to either cAMP-responsive element-binding protein or AP-1. These results suggest that thyroglobulin gene expression in FRTL-5 cells may be mediated by nuclear factors that are induced by cAMP in contrast to other genes (e.g. c-fos) whose activation involves post-translational modification of the pre-existing proteins specific for cAMP-responsive element.
Lee
N T
NT
Department of Biochemistry, University of North Carolina, Chapel Hill 27599-7260.
Nayfeh
S N
SN
Chae
C B
CB
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D009687:Nuclear Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP