Identification of thyroid hormone response elements in the human fatty acid synthase promoter
| Autor: | Subrahmanyam S. Chirala, Salih J. Wakil, Shunbin Xiong, Matthew H. Hsu |
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| Rok vydání: | 1998 |
| Předmět: |
Thyroid Hormones
Receptors Retinoic Acid Biology Cell Line Thyroid hormone receptor beta medicine Humans Promoter Regions Genetic Hormone response element Reporter gene Receptors Thyroid Hormone Multidisciplinary Thyroid hormone receptor Triiodothyronine Base Sequence Thyroid Biological Sciences Molecular biology Retinoid X Receptors medicine.anatomical_structure Oligodeoxyribonucleotides Biochemistry Thyroid hormone receptor alpha Fatty Acid Synthases PAX8 Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 95:12260-12265 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.95.21.12260 |
| Popis: | To investigate the regulation of the human fatty acid synthase gene by the thyroid hormone triiodothyronine, various constructs of the human fatty acid synthase promoter and the luciferase reporter gene were transfected in combination with plasmids expressing the thyroid hormone and the retinoid X receptors in HepG2 cells. The reporter gene was activated 25-fold by the thyroid hormone in the presence of the thyroid hormone receptor. When both the thyroid hormone and the retinoid X receptors were expressed in HepG2 cells, there was about a 100-fold increase in reporter gene expression. 5′-Deletion analysis disclosed two thyroid hormone response elements, TRE1 (nucleotides −870 to −650) and TRE2 (nucleotides −272 to −40), in the human fatty acid synthase promoter. The presence of thyroid hormone response elements in these two regions of the promoter was confirmed by cloning various fragments of these two regions in the minimal thymidine kinase promoter−luciferase reporter gene plasmid construct and determining reporter gene expression. The results of this cloning procedure and those of electrophoretic mobility shift assays indicated that the sequence GGGTTAcgtcCGGTCA (nucleotides −716 to −731) represents TRE1 and that the sequence GGGTCC (nucleotides −117 to −112) represents TRE2. The sequence of TRE1 is very similar to the consensus sequence of the thyroid hormone response element, whereas the sequence of TRE2 contains only a half-site of the thyroid hormone response element consensus motif because it lacks the direct repeat. The sequences on either side of TRE2 seem to influence its response to the thyroid hormone and retinoid X receptors. |
| Databáze: | OpenAIRE |
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