Gene-specific recruitment of positive and negative elongation factors during stimulated transcription of the MKP-1 gene in neuroendocrine cells
| Autor: | Silvia Tortola, Werner Schlegel, Isabelle Piuz, Toshitsugu Fujita, Stephan Ryser |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Transcriptional Activation
Transcription Genetic DNA polymerase II RNA polymerase II Cell Cycle Proteins Gene Expression Regulation Enzymologic Cell Line Immediate-Early Proteins 03 medical and health sciences Exon 0302 clinical medicine Transcription (biology) Protein Phosphatase 1 Genetics Phosphoprotein Phosphatases Serine Animals Enzyme Inhibitors Transcription factor Molecular Biology Thyrotropin-Releasing Hormone 030304 developmental biology 0303 health sciences biology Models Genetic Dual Specificity Phosphatase 1 DSIF Molecular biology Cyclin-Dependent Kinase 9 Protein Structure Tertiary Rats Elongation factor 030220 oncology & carcinogenesis Pituitary Gland biology.protein Cyclin-dependent kinase 9 RNA Polymerase II Protein Tyrosine Phosphatases Transcriptional Elongation Factors Dichlororibofuranosylbenzimidazole Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | MAP kinase phosphatase-1 (MKP-1) controls nuclear MAP kinase activity with important consequences on cell growth or apoptosis. MKP-1 transcription is initiated constitutively but elongation is blocked within exon 1. It is unclear how induction of MKP-1 is controlled. Here, we report that the transcriptional elongation factors P-TEFb, DSIF and NELF regulate MKP-1 transcription in the pituitary GH4C1 cell line. Prior to stimulation, DSIF, NELF and RNA polymerase II (pol II) associate with the promoter-proximal region of the MKP-1 gene upstream of the elongation block site. Thyrotropin-releasing hormone (TRH) leads to recruitment of P-TEFb along the whole gene and a marked increase of DSIF and pol II downstream of the elongation block site, whereas NELF remains confined to the promoter-proximal region. 5,6-Dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) an inhibitor of P-TEFb eliminated TRH stimulation of MKP-1 transcription. DRB specifically inhibited TRH-induced recruitment of DSIF and P-TEFb to the MKP-1 gene. Furthermore, DRB treatment eliminated TRH-induced progression along the MKP-1 gene of pol II phosphorylated on Ser-2 of its CTD. These results indicate that P-TEFb is essential for gene-specific stimulated transcriptional elongation in mammalian cells via mechanisms which involve the activation of the DSIF-NELF complex and Ser-2 phosphorylation of pol II. |
| Databáze: | OpenAIRE |
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