Oct-2 forms a complex with Oct-1 on the iNOS promoter and represses transcription by interfering with recruitment of RNA PolII by Oct-1

Fatima Bentrari, Aurelie Chantôme, Andrew Knights, Jean-François Jeannin, Alena Pance

Research output: Contribution to journalArticlepeer-review

Abstract

Oct-1 (POU2f1) and Oct-2 (POU2f2) are members of the POU family of transcription factors. They recognize the same DNA sequence but fulfil distinct functions: Oct-1 is ubiquitous and regulates a variety of genes while Oct-2 is restricted to B-cells and neurones. Here we examine the interplay and regulatory mechanisms of these factors to control the inducible nitric oxide synthase (iNOS, NOS2). Using two breast cancer cell lines as a comparative model, we found that MCF-7 express iNOS upon cytokine stimulation while MDA-MB-231 do not. Oct-1 is present in both cell lines but MDA-MB-231 also express high levels of Oct-2. Manipulation of Oct-2 expression in these cell lines demonstrates that it is directly responsible for the repression of iNOS in MDA-MB-231. In MCF-7 cells Oct-1 binds the iNOS promoter, recruits RNA PolII and triggers initiation of transcription. In MDA-MB-231 cells, both Oct-1 and Oct-2 bind the iNOS promoter, forming a higher-order complex which fails to recruit RNA PolII, and as a consequence iNOS transcription does not proceed. Unravelling the mechanisms of transcription factor activity is paramount to the understanding of gene expression patterns that determine cell behaviour.

Original languageEnglish
Pages (from-to)9757-65
Number of pages9
JournalNucleic Acids Research
Volume43
Issue number20
DOIs
Publication statusPublished - 16 Nov 2015

Keywords

  • Breast Neoplasms/genetics
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Nitric Oxide Synthase Type II/genetics
  • Octamer Transcription Factor-1/metabolism
  • Octamer Transcription Factor-2/metabolism
  • Promoter Regions, Genetic
  • RNA Polymerase III/metabolism
  • Repressor Proteins/metabolism
  • Transcription, Genetic

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