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Series GSE147308 Query DataSets for GSE147308
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
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.
 
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
 
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
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (8)
GSM4425562 ATAC-seq_THP1_PMA_ctrl_unstimulated
GSM4425563 ATAC-seq_THP1_PMA_ctrl_LPS_1hr
GSM4425564 ATAC-seq_THP1_PMA_ctrl_LPS_3hr
This SubSeries is part of SuperSeries:
GSE147314 Chromatin accessibility dictates specific transcriptional response by different cells of the innate immune system
Relations
BioProject PRJNA613717
SRA SRP253517

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE147308_RAW.tar 2.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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