|
| Status |
Public on Dec 12, 2011 |
| Title |
Modulation of NF-kB-Dependent Gene Transcription Using Programmable DNA Minor Groove Binders |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
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
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| Contributor(s) |
Raskatov JA, Meier JL, Puckett JW, Yang FT, Ramakrishnan P, Dervan PB |
| Citation(s) |
22203967 |
| Submission date |
Dec 09, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Jevgenij A. Raskatov |
| E-mail(s) |
raskatov@caltech.edu
|
| Phone |
6263956084
|
| Organization name |
CalTech
|
| Department |
CCE
|
| Lab |
Dervan
|
| Street address |
1200 EAST CALIFORNIA BOULEVARD
|
| City |
PASADENA |
| State/province |
California |
| ZIP/Postal code |
91125 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
|
| Samples (11)
|
| GSM847878 |
RNA-seq Non-induced Replicate 1 |
| GSM847879 |
RNA-seq Non-induced Replicate 2 |
| GSM847880 |
RNA-seq Induced Replicate 1 |
| GSM847881 |
RNA-seq Induced Replicate 2 |
| GSM847882 |
RNA-seq Induced and PA-treated Replicate 1 |
| GSM847883 |
RNA-seq Induced and PA-treated Replicate 2 |
| GSM847884 |
RNA-seq Induced and PS1145-treated Replicate 1 |
| GSM847885 |
RNA-seq Induced and PS1145-treated Replicate 2 |
|
| Relations |
| SRA |
SRP009790 |
| BioProject |
PRJNA151489 |
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