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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 30, 2020 |
| Title |
Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [MEFs_2] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
NFkB RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (ChIPseq) and functional (RNAseq in knockouts) datasets. We then dissected each gene's regulatory strategy by testing RelA variants in a novel primary-cell genetic complementation assay. All endogenous target genes required that RelA makes DNA-base-specific contacts, and none could be activated by the DNA binding domain alone. However, endogenous target genes differed widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic timecourse data we reveal gene-specific synergy and redundancy of TA1 and TA2. Given that post-translational modifications control TA1 activity and intrinsic affinity for coactivators determines TA2 activity, the differential TA logics suggests context-dependent vs. context-independent control of endogenous RelA-target genes. While some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NFkB RelA core response.
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| Overall design |
Total RNA extracted from primary mouse embryonic fibroblasts stimulated with LPS, Poly(I:C), and TNF.
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| Contributor(s) |
Ngo KA, Hoffmann A |
| Citation(s) |
32101750 |
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| Submission date |
Jun 12, 2019 |
| Last update date |
Mar 16, 2020 |
| Contact name |
Kim Ngo |
| E-mail(s) |
kango@ucla.edu
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| Organization name |
University of California, Los Angeles
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| Department |
MIMG
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| Lab |
Alexander Hoffmann
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| Street address |
611 Charles E Young Dr. East
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (38)
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| GSM3884927 |
WT MEFs TNF 3hr, replicate 1 |
| GSM3884928 |
WT MEFs TNF 8hr, replicate 1 |
| GSM3884929 |
WT MEFs 0hr, replicate 2 |
| GSM3884930 |
WT MEFs TNF 0.5hr, replicate 2 |
| GSM3884931 |
WT MEFs TNF 1hr, replicate 2 |
| GSM3884932 |
WT MEFs TNF 3hr, replicate 2 |
| GSM3884933 |
WT MEFs TNF 8hr, replicate 2 |
| GSM3884934 |
RelA-TA-KI MEFs 0hr, replicate 1 |
| GSM3884935 |
RelA-TA-KI MEFs TNF 0.5hr, replicate 1 |
| GSM3884936 |
RelA-TA-KI MEFs TNF 1hr, replicate 1 |
| GSM3884937 |
RelA-TA-KI MEFs TNF 3hr, replicate 1 |
| GSM3884938 |
RelA-TA-KI MEFs TNF 8hr, replicate 1 |
| GSM3884939 |
RelA-TA-KI MEFs 0hr, replicate 2 |
| GSM3884940 |
RelA-TA-KI MEFs TNF 0.5hr, replicate 2 |
| GSM3884941 |
RelA-TA-KI MEFs TNF 1hr, replicate 2 |
| GSM3884942 |
RelA-TA-KI MEFs TNF 3hr, replicate 2 |
| GSM3884943 |
RelA-TA-KI MEFs TNF 8hr, replicate 2 |
| GSM3884944 |
WT MEFs LPS 0hr |
| GSM3884945 |
WT MEFs LPS 0.5hr |
| GSM3884946 |
WT MEFs LPS 1hr |
| GSM3884947 |
WT MEFs LPS 3hr |
| GSM3884948 |
WT MEFs LPS 8hr |
| GSM3884949 |
WT MEFs Poly(I:C) 0.5hr |
| GSM3884950 |
WT MEFs Poly(I:C) 1hr |
| GSM3884951 |
WT MEFs Poly(I:C) 3hr |
| GSM3884952 |
WT MEFs Poly(I:C) 8hr |
| GSM3884953 |
RelA-TA-KI MEFs LPS 0hr |
| GSM3884954 |
RelA-TA-KI MEFs LPS 0.5hr |
| GSM3884955 |
RelA-TA-KI MEFs LPS 1hr |
| GSM3884956 |
RelA-TA-KI MEFs LPS 3hr |
| GSM3884957 |
RelA-TA-KI MEFs LPS 8hr |
| GSM3884958 |
RelA-TA-KI MEFs Poly(I:C) 0.5hr |
| GSM3884959 |
RelA-TA-KI MEFs Poly(I:C) 1hr |
| GSM3884960 |
RelA-TA-KI MEFs Poly(I:C) 3hr |
| GSM3884961 |
RelA-TA-KI MEFs Poly(I:C) 8hr |
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| This SubSeries is part of SuperSeries: |
| GSE132540 |
Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics |
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| Relations |
| BioProject |
PRJNA548592 |
| SRA |
SRP201264 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132654_WT_RelA-TA-KI.MEFs_LPS_polyIC_non-normalized-counts.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
| GSE132654_WT_RelA-TA-KI.MEFs_TNF_non-normalized-counts.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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