Ca2+-dependent regulation of calcitonin gene expression by the transcriptional repressor DREAM

Miho Matsuda, Tada Aki Yamamoto, Masato Hirata

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)


Calcitonin (CT), whose secretion from thyroid glands is regulated by increases in the concentration of extracellular Ca2+, is a well-known hormone that regulates calcium homeostasis. However, the molecular mechanisms underlying the gene expression dependent on Ca2+ have not been clarified. The downstream regulatory element (DRE) antagonist modulator (DREAM) was recently identified as a Ca2+-dependent transcriptional repressor. In the present study, we investigated the possible involvement of DREAM in the regulation of CT gene expression and secretion. A luciferase assay using TT cells, a thyroid carcinoma cell line, showed that a particular region in the CT gene promoter repressed the promoter activity under basal conditions but induced the activity when the Ca2+ concentration was increased. We found two DRE sequences in a region located upstream from the transcription start site. Gel retardation assay confirmed that DREAM bound to the CT-DRE and also indicated that DREAM bound to the DRE in a Ca2+-dependent manner. We generated stable transfectants of TT cells with wild-type or mutant DREAM, which lacked the responsiveness to Ca2+ changes. In contrast to the wild type, overexpression of the mutant DREAM inhibited the increase in CT secretion induced by a calcium ionophore. The addition of forskolin to increase cAMP activated the CT promoter, probably by the interaction of DREAM with cAMP-responsive element binding proteins, independent on the activation by Ca2+. Together, these results suggest that DREAM plays an important role in human CT gene expression in a Ca2+- and cAMP-dependent manner.

出版ステータス出版済み - 2006

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学


「Ca2+-dependent regulation of calcitonin gene expression by the transcriptional repressor DREAM」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。