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 language | English |
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Pages (from-to) | 9757-65 |
Number of pages | 9 |
Journal | Nucleic Acids Research |
Volume | 43 |
Issue number | 20 |
DOIs | |
Publication status | Published - 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