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Series GSE151015 Query DataSets for GSE151015
Status Public on Sep 15, 2020
Title The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the stable epigenomic program of alternative macrophage polarization
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream of the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, Early Growth Response 2 (EGR2), bridging the early-transient and late-stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA-polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages.
 
Overall design Transcriptomic and epigenetic profiling of IL-4 treated bone-marrow derived macrophages (BMDMs), using high throughput sequencing (RNA-seq, ChIP-seq and ATAC-seq).
 
Contributor(s) Halasz L, Nagy L
Citation(s) 33060136
Submission date May 21, 2020
Last update date Dec 29, 2020
Contact name Laszlo Halasz
E-mail(s) laszlo.halasz@jhmi.edu
Phone 7276416811
Organization name Johns Hopkins University
Department Institute for Fundamental Biomedical Research
Lab Nagy Lab
Street address 600 5th Ave S
City Saint Petersburg
State/province Florida
ZIP/Postal code 33701
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (72)
GSM4564251 Wild-type unstimulated BMDM RNA-seq replicate 1
GSM4564252 Wild-type unstimulated BMDM RNA-seq replicate 2
GSM4564253 Wild-type unstimulated BMDM RNA-seq replicate 3
Relations
BioProject PRJNA634372
SRA SRP262690

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Supplementary file Size Download File type/resource
GSE151015_RAW.tar 15.1 Gb (http)(custom) TAR (of BW)
GSE151015_mm_BMDM_Egr2_RNAseq_CPM_counts.txt.gz 2.0 Mb (ftp)(http) TXT
GSE151015_mm_BMDM_Egr2_RNAseq_raw_counts.txt.gz 731.5 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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