Transcriptional repressor DREAM interacts with thyroid transcription factor-1 and regulates thyroglobulin gene expression.
Tissue-specific gene expression depends on the interaction between tissue-specific and general transcription factors. DREAM is a Ca2+-dependent transcriptional repressor widely expressed in the brain where it participates in nociception through its control of prodynorphin gene expression. In the periphery, DREAM is highly expressed in the thyroid gland, the immune system, and the reproductive organs. Here, we show that DREAM interacts with thyroid-specific transcription factor TTF-1 and regulates the expression of the thyroglobulin (Tg) gene. The mechanism also involves binding of DREAM to the thyroglobulin promoter and blockage of TTF-1-mediated transactivation. The TSH/cAMP pathway and Ca2+ signaling regulate DREAM-mediated transcriptional repression of the thyroglobulin gene. Furthermore, chromatin immunoprecipitation experiments in FRTL-5 cells confirmed that Tg is a bona fide target gene for DREAM transrepression in thyroid follicular cells.
Rivas
Marcos
M
Dpto. Biología Molecular y Celular, Centro Nacional de Biotecnología, CSIC 28049 Madrid, Spain.
Mellström
Britt
B
Naranjo
José R
JR
Santisteban
Pilar
P
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004347:Drug Interactions; D015870:Gene Expression; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000737:chemistry; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D002135:Calcium-Binding Proteins; C496749:KCNIP3 protein, human; C496760:Kcnip3 protein, rat; D051605:Kv Channel-Interacting Proteins; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D000242:Cyclic AMP; D002118:Calcium