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| Status |
Public on Apr 19, 2018 |
| Title |
Runx3 pioneers chromatin accessibility of cis-regulatory landscapes that drive memory CTL formation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
T cell receptor (TCR) stimulation of naïve CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naïve cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 controls de novo access to memory CTL-specific cistromes prior to the first cell division, and is essential for memory CTL differentiation. Runx3 specifically promotes accessibility of cis-acting regions highly enriched with IRF, bZIP and Prdm1-like family TF motifs, upregulates IRF4 and establishes feed-forward transcriptional circuits that induce fundamental CTL attributes in memory precursor cells. Runx3 drives uncoupling from the naïve cell state, but subsequently restrains terminal differentiation of nascent CTL by preventing high expression of the TF T-bet and slowing effector cell proliferation. Enforced Runx3 expression enhances memory CTL differentiation and increases their numbers during iterative infections. Thus, Runx3 functions in a pioneering role to initialize and then ensure memory CTL differentiate.
This SuperSeries is composed of the SubSeries listed below.
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| Overall design |
Refer to individual Series
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| Web link |
https://www.ncbi.nlm.nih.gov/pubmed/29669249
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| |
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| Contributor(s) |
Getzler AJ, Diao H, Wang D, Pipkin ME |
| Citation(s) |
29669249 |
| |
| Submission date |
Feb 26, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Adam Getzler |
| E-mail(s) |
agetzler@scripps.edu
|
| Organization name |
TSRI-FL
|
| Street address |
130 Scripps Way
|
| City |
Jupiter |
| State/province |
FL |
| ZIP/Postal code |
33458-5284 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (54)
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| This SuperSeries is composed of the following SubSeries:
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| GSE111135 |
Chromatin Associated RNA-Seq of CD8+ T cells expressing different levels of Runx3 in a cell culture model of CTL differentiation [Chr Assoc] |
| GSE111138 |
RNA-Seq of CD8+ T cells expressing different levels of Runx3 in during LCMV infection (in vivo) |
| GSE111143 |
RNA-Seq of CD8+ T cells during LCMV infection [WT infection] |
| GSE111144 |
ATAC-Seq of CD8+ T cells during activaion in vitro over the course 24 hours with and without Runx3 |
|
| Relations |
| BioProject |
PRJNA436011 |
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