Inhibition of ERα-mediated trans-activation of human coagulation factor XII gene by heteromeric transcription factor NF-Y

Antonella Farsetti, Michela Narducci, Fabiola Moretti, Simona Nanni, Roberto Mantovani, Ada Sacchi, Alfredo Pontecorvi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3380-3388
Number of pages9
JournalEndocrinology
Volume142
Issue number8
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Farsetti, A., Narducci, M., Moretti, F., Nanni, S., Mantovani, R., Sacchi, A., & Pontecorvi, A. (2001). Inhibition of ERα-mediated trans-activation of human coagulation factor XII gene by heteromeric transcription factor NF-Y. Endocrinology, 142(8), 3380-3388. https://doi.org/10.1210/en.142.8.3380