Modulation of NF-κB-dependent gene transcription using programmable DNA minor groove binders.
- Authors
- Type
- Published Article
- Journal
- Proceedings of the National Academy of Sciences
- Publisher
- Proceedings of the National Academy of Sciences
- Volume
- 109
- Issue
- 4
- Pages
- 1023–1028
- Identifiers
- DOI: 10.1073/pnas.1118506109
- Source
- UCSC Aging biomedical-ucsc
- License
- Unknown
Abstract
Nuclear factor κB (NF-κB) is a transcription factor that regulates various aspects of immune response, cell death, and differentiation as well as cancer. In this study we introduce the Py-Im polyamide 1 that binds preferentially to the sequences 5 -WGGWWW-3 and 5 GGGWWW-3 . The compound is capable of binding to κB sites and reducing the expression of various NF-κB-driven genes including IL6 and IL8 by qRT-PCR. Chromatin immunoprecipitation experiments demonstrate a reduction of p65 occupancy within the proximal promoters of those genes. Genome-wide expression analysis by RNA-seq compares the DNA-binding polyamide with the well-characterized NF-κB inhibitor PS1145, identifies overlaps and differences in affected gene groups, and shows that both affect comparable numbers of TNF-α-inducible genes. Inhibition of NF-κB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists.