Participation of Ets transcription factors in the glucocorticoid response of the rat tyrosine aminotransferase gene
| Autor: | Jeanne Roux, Thierry Grange, J Ghysdael, Raymond Pictet, Maria Lluisa Espinás |
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| Rok vydání: | 1994 |
| Předmět: |
Molecular Sequence Data
Gene Expression RNA polymerase II Biology Transfection Cell Line Proto-Oncogene Protein c-ets-1 Mice Liver Neoplasms Experimental Receptors Glucocorticoid Glucocorticoid receptor Tyrosine aminotransferase Transcription (biology) Proto-Oncogene Proteins Sequence Homology Nucleic Acid Consensus Sequence Tumor Cells Cultured Animals Binding site Promoter Regions Genetic Transcription factor Molecular Biology Tyrosine Transaminase Binding Sites COS cells Base Sequence Proto-Oncogene Proteins c-ets DNA Cell Biology Molecular biology Rats Chromatin Oligodeoxyribonucleotides biology.protein RNA Polymerase II Transcription Factors Research Article |
| Zdroj: | Molecular and Cellular Biology. 14:4116-4125 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.14.6.4116 |
| Popis: | We have previously shown that two remote glucocorticoid-responsive units (GRUs) of the rat tyrosine aminotransferase (TAT) gene contain multiple binding sites for several transcription factor families, including the glucocorticoid receptor (GR). We report here the identification of two novel binding sites for members of the Ets family of transcription factors in one of these GRUs. One of these binding sites overlaps the major GR-binding site (GRBS), whereas the other is located in its vicinity. Inactivation of the latter binding site leads to a twofold reduction of the glucocorticoid response, whereas inactivation of the site overlapping the GRBS has no detectable effect. In vivo footprinting analysis reveals that the active site is occupied in a glucocorticoid-independent manner, in a TAT-expressing cell line, even though it is located at a position where there is a glucocorticoid-dependent alteration of the nucleosomal structure. This same site is not occupied in a cell line that does not express TAT but expresses Ets-related DNA-binding activities, suggesting the existence of an inhibitory effect of chromatin structure at a hierarchical level above the nucleosome. The inactive Ets-binding site that overlaps the GRBS is not occupied even in TAT-expressing cells. However, this same overlapping site can confer Ets-dependent stimulation of both basal and glucocorticoid-induced levels when it is isolated from the GRU and duplicated. Ets-1 expression in COS cells mimics the activity of the Ets-related activities present in hepatoma cells. These Ets-binding sites could participate in the integration of the glucocorticoid response of the TAT gene with signal transduction pathways triggered by other nonsteroidal extracellular stimuli. |
| Databáze: | OpenAIRE |
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