The human neuroendocrine thyrotropin-releasing hormone receptor promoter is activated by the haematopoietic transcription factor c-Myb
| Autor: | Lars Helgeland, Per I. Høvring, Christophe Orvain, Kaare M. Gautvik, Kristin B. Andersson, Ase-Karine Fjeldheim, Odd S. Gabrielsen, Vilborg Matre |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Thymus Gland Biology Response Elements Transfection Biochemistry Cell Line Proto-Oncogene Proteins c-myb Transactivation Anterior pituitary Thyrotropin-releasing hormone receptor medicine Animals Humans MYB RNA Messenger Promoter Regions Genetic Receptor Molecular Biology Transcription factor Hormone response element Binding Sites Receptors Thyrotropin-Releasing Hormone Cell Biology Hematopoietic Stem Cells Neurosecretory Systems Molecular biology Introns Rats medicine.anatomical_structure Gene Expression Regulation COS Cells Research Article HeLa Cells Plasmids Protein Binding |
| Zdroj: | Biochemical Journal. 372:851-859 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Thyrotropin-releasing hormone (TRH) receptor (TRHR) is a G-protein-coupled receptor playing a crucial role in the anterior pituitary where it controls the synthesis and secretion of thyroid-stimulating hormone and prolactin. Its widespread presence not only in the central nervous system, but also in peripheral tissues, including thymus, indicates other important, but unknown, functions. One hypothesis is that the neuropeptide TRH could play a role in the immune system. We report here that the human TRHR promoter contains 11 putative response elements for the haematopoietic transcription factor c-Myb and is highly Myb-responsive in transfection assays. Analysis of Myb binding to putative response elements revealed one preferred binding site in intron 1 of the receptor gene. Transfection studies of promoter deletions confirmed that this high-affinity element is necessary for efficient Myb-dependent transactivation of reporter plasmids in CV-1 cells. The Myb-dependent activation of the TRHR promoter was strongly suppressed by expression of a dominant negative Myb–Engrailed fusion. In line with these observations, reverse transcriptase PCR analysis of rat tissues showed that the TRHR gene is expressed both in thymocytes and bone marrow. Furthermore, specific, high-affinity TRH agonist binding to cell-surface receptors was demonstrated in thymocytes and a haematopoietic cell line. Our findings imply a novel functional link between the neuroendocrine and the immune systems at the level of promoter regulation. |
| Databáze: | OpenAIRE |
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