Inhibition of ERα-MediatedTrans-Activation of Human Coagulation Factor XII Gene by Heteromeric Transcription Factor NF-Y
| Autor: | Fabiola Moretti, Antonella Farsetti, Ada Sacchi, Simona Nanni, Alfredo Pontecorvi, Roberto Mantovani, Michela Narducci |
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| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Transcription Genetic Molecular Sequence Data Response element CAAT box Estrogen receptor Coagulation Factor XII Biology Mice Endocrinology Tumor Cells Cultured Animals Humans Protein Isoforms Promoter Regions Genetic Transcription factor Hormone response element Factor XII Base Sequence Estradiol Estrogen Receptor alpha 3T3 Cells DNA Molecular biology Protein Structure Tertiary CCAAT-Binding Factor Gene Expression Regulation Receptors Estrogen Transcription preinitiation complex hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology (Philadelphia) 142 (2001): 3380–3388. info:cnr-pdr/source/autori:Farsetti A., Narducci M., Moretti F., Nanni S., Mantovani R., Sacchi A., Pontecorvi A./titolo:Inhibition of ERalpha-mediated trans-activation of human coagulation factor XII gene by heteromeric transcription factor NF-Y./doi:/rivista:Endocrinology (Philadelphia)/anno:2001/pagina_da:3380/pagina_a:3388/intervallo_pagine:3380–3388/volume:142 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.142.8.8345 |
| Popis: | Human coagulation factor XII promoter contains an estrogen response element that mediates ligand-activated ERa induction of coagulation factor XII gene expression. The 3*-half of coagulation factor XII-estrogen response element overlaps a putative CCAAT box, the widespread regulatory element specifically recognized by the heteromeric transcription factor NF-Y. Transient cotransfection of NF-Y and ERa results in strong inhibition of estrogen stimulation of coagulation factor XII promoter activity. NF-Y antagonism is primarily exerted by the NF-YA subunit and does not require binding to the CCAAT element, as NF-YA mutants with impaired DNA binding capacity retain the ability to inhibit ERa trans-activation. EMSAs with increasing concentrations of recombinant NF-Y do not detect the formation of NF-Y-DNA complexes or show impairment of ERa binding to estrogen response element. Immunoprecipitation of whole cell extracts with anti-ERa antibody reveals an in vivo association between the two transcription factors, which is abolished by deletion of the NF-YA carboxyl-terminus. In functional experiments with sequential NF-YA deletion mutants the HAP2-homology region appears essential in eliciting NF-YA antagonistic activity. In conclusion, our results demonstrate that heteromeric transcription factor NF-Y inhibits estrogen induction of coagulation factor XII promoter in a DNA binding-independent fashion and suggest a novel role for NF-Y as a partner for the ERa transcription complex. (Endocrinology 142: 3380 ‐3388, 2001) |
| Databáze: | OpenAIRE |
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