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| Status |
Public on Aug 22, 2020 |
| Title |
Immune differentiation regulator p100 tunes NF-kB responses to TNF |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Stringent regulation of TNF signaling prevents aberrant inflammation. TNF engages the canonical NF-kB pathway for activating the RelA:p50 heterodimer, which mediates specific expressions of pro-inflammatory and immune response genes. Importantly, the NF-kB system discriminates between time-varied TNF inputs. Negative feedback regulators of the canonical pathway, including IkBa, thought to ensure transient RelA:p50 responses to brief TNF stimulations. The noncanonical NF-kB pathway controls a separate RelB activity associated with immune differentiation. In a systems modeling approach, we uncovered an unexpected role of p100, a constituent of the noncanonical pathway, in TNF signaling. Brief TNF stimulation of p100-deficient cells produced an additional late NF-kB activity composed of the RelB:p50 heterodimer, which distorted the TNF-induced gene-expression program. Periodic TNF pulses augmented this RelB:p50 activity, which was reinforced by NF-kB-dependent RelB synthesis. In sum, the NF-kB system seems to engage distantly related molecular species for enforcing dynamical and gene controls of immune-activating TNF signaling.
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| Overall design |
There are 9 samples in total. Every time point has two replictes. The Input sample is the control and it is the combined input sample from the two replicates.
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| Contributor(s) |
Zhao M, Singh A, Joy J, De S, Sen R |
| Citation(s) |
31134075 |
| |
| Submission date |
Sep 14, 2018 |
| Last update date |
Aug 25, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
|
| Department |
Laboratory of Genetics and Genomics
|
| Lab |
Computational Biology & Genomics Core
|
| Street address |
251 Bayview Blvd
|
| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA490828 |
| SRA |
SRP161750 |
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