Inhibition of ERα-mediated trans-activation of human coagulation factor XII gene by heteromeric transcription factor NF-Y
Articolo
Data di Pubblicazione:
2001
Citazione:
Inhibition of ERα-mediated trans-activation of human coagulation factor XII gene by heteromeric transcription factor NF-Y / A. Farsetti, M. Narducci, F. Moretti, S. Nanni, R. Mantovani, A. Sacchi, A. Pontecorvi. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - 142:8(2001 Aug), pp. 3380-3388.
Abstract:
Human coagulation factor Xii promoter contains an estrogen response element that mediates ligand-activated Erα 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 ERα 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 ERα trans-activation. EMSAs with increasing concentrations of recombinant NF-Y do not detect the formation of NF-Y-DNA complexes or show impairment of ERα binding to estrogen response element. Immunoprecipitation of whole cell extracts with anti-ERα 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 ERα transcription complex.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
3T3 Cells ; Animals ; Base Sequence ; CCAAT-Binding Factor ; DNA ; Estradiol ; Estrogen Receptor Alpha ; Factor XII ; Gene Expression Regulation ; Humans ; Mice ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Isoforms ; Protein Structure, Tertiary ; Receptors, Estrogen ; Transcription, Genetic ; Transcriptional Activation ; Tumor Cells, Cultured
Elenco autori:
A. Farsetti, M. Narducci, F. Moretti, S. Nanni, R. Mantovani, A. Sacchi, A. Pontecorvi
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