Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

• Published in: The Journal of biological chemistry Vol. 279; no. 32; pp. 33114 - 33122
• Main Authors: Rivas, Marcos, Mellström, Britt, Naranjo, José R., Santisteban, Pilar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.08.2004; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Base Sequence; Binding Sites; Calcium - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - physiology; Cell Line; Cyclic AMP - physiology; DNA - chemistry; DNA - metabolism; Drug Interactions; Gene Expression; Gene Expression Regulation; HeLa Cells; Humans; Kv Channel-Interacting Proteins; Nuclear Proteins - physiology; Promoter Regions, Genetic - genetics; Rats; Repressor Proteins - genetics; Repressor Proteins - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Signal Transduction; Thyroglobulin - genetics; Thyroid Gland - chemistry; Thyroid Nuclear Factor 1; Thyrotropin - pharmacology; Transcription Factors - physiology; Transcriptional Activation; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M403526200

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.