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| Status |
Public on Mar 16, 2021 |
| Title |
IRF1 governs the differential Interferon-Stimulated Gene responses in human monocytes and macrophages by regulating chromatin accessibility (ATAC - IRF1 KO THP-1) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Myeloid lineage cells use TLRs to recognize and respond to diverse microbial ligands. Although unique transcription factors dictate the outcome of specific TLR signaling, whether lineage-specific differences exist to further modulate the quality of TLR-induced inflammation remains unclear. Comprehensive analysis of global gene transcription in human monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells stimulated with various TLR ligands identifies multiple lineage-specific, TLR-responsive gene programs. Monocytes are hyperresponsive to TLR7/8 stimulation that correlates with higher expression of the receptors. While macrophages and monocytes express similar levels of TLR4, macrophages, but not monocytes, upregulate Interferon-Stimulated Genes (ISGs) in response to TLR4 stimulation. We find that TLR4 signaling in macrophages uniquely engages transcription factor IRF1, which facilitates opening of ISG loci for transcription. This study provides a critical mechanistic basis for lineage-specific TLR responses and uncovers IRF1 as a master epigenetic regulator for the ISG transcriptional program in human macrophages.
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| Overall design |
ATAC-seq anlaysis of epigenomic changes in PMA-differentiated control clonal THP-1 cell line and PMA-differentiated IRF1 deficient clonal THP-1 cell line unstimulated or stimulated with LPS for 1, 3 or 6 hours
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| Contributor(s) |
Song R, Dozmorov I, Malladi V, Liang C, Arana C, Wakeland B, Pasare C, Wakeland EK |
| Citation(s) |
33761354 |
| |
| Submission date |
Mar 20, 2020 |
| Last update date |
Apr 01, 2021 |
| Contact name |
Edward Wakeland |
| Organization name |
UT Southwestern Medical Center
|
| Department |
Immunology
|
| Street address |
5323 Harry Hines Blvd
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9093 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE147314 |
Chromatin accessibility dictates specific transcriptional response by different cells of the innate immune system |
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| Relations |
| BioProject |
PRJNA613717 |
| SRA |
SRP253517 |
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