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Modulation of NF-kB-Dependent Gene Transcription Using Programmable DNA Minor Groove Binders

ABSTRACT: Nuclear factor kappaB (NF-kB) 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 kB sites and reducing the expression of various NF-kB 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-kB inhibitor PS1145, identifying overlaps and differences in affected gene groups and showing that both affect comparable numbers of TNFa inducible genes. Inhibition of NF-kB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34329 | GEO | 2011/12/12

SECONDARY ACCESSION(S): PRJNA151489

REPOSITORIES: GEO

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Modulation of NF-kB-Dependent Gene Transcription Using Programmable DNA Minor Groove Binders

Project description:Nuclear factor kappaB (NF-kB) 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 kB sites and reducing the expression of various NF-kB 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-kB inhibitor PS1145, identifying overlaps and differences in affected gene groups and showing that both affect comparable numbers of TNFa inducible genes. Inhibition of NF-kB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists. A549 cells were treated with either a Py-Im polyamide or PS1145, subsequently induced with TNFa and compared with the untreated TNFa induced and the basal state by RNAseq. The NF-kB binding motif was derived by ChIP-seq

2011-12-12 | E-GEOD-34329 | biostudies-arrayexpress

Modulation of NF-κB-dependent gene transcription using programmable DNA minor groove binders.

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2024-05-09 | PXD037534 | JPOST Repository

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