The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-κB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1β production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli.
Pubmed ID: 29343442 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsA commercial graphing software company that offers scientific software for statistical analyses, curve fitting and data analysis. It offers four programs: Prism, InStat, StatMate and QuickCalcs.
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsInternational functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.
View all literature mentionsCompute differentially bound sites from multiple ChIP-seq experiments using affinity (quantitative) data. Also enables occupancy (overlap) analysis and plotting functions.
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsA powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.
View all literature mentionsSoftware application that can be used for converting Eland, Maq (.map), BED or other files into WIG files and identifying areas of enrichment (ChIP-Seq analysis).
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Mouse ECF-L / CHI3L3
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentionsThis monoclonal targets NLRP3/NALP3
View all literature mentionsThis unknown targets Widely expressed. Synthetic peptide: C-NEFYDGDHDNDKESDVEI conjugated to KLH, corresponding to amino acids 411-428 of Human HDAC3.
View all literature mentionsThis polyclonal targets HDAC1 - ChIP Grade
View all literature mentionsThis monoclonal targets iNOS
View all literature mentionsThis polyclonal targets PYCARD
View all literature mentionsThis polyclonal targets POLR2AphosphoS2
View all literature mentionsThis monoclonal targets Caspase-1
View all literature mentionsThis polyclonal targets Mouse IL-1 beta / IL-1F2
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets RNA polymerase II CTD repeat YSPTSPS (phospho S5) antibody - ChIP Grade
View all literature mentionsThis polyclonal targets HDAC2 antibody - ChIP Grade
View all literature mentionsThis polyclonal targets IRF8
View all literature mentionsThis polyclonal targets PU.1 (Spi-1) (T-21)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsThis monoclonal targets iNOS
View all literature mentionsThis polyclonal targets PYCARD
View all literature mentionsThis polyclonal targets POLR2AphosphoS2
View all literature mentionsThis monoclonal targets Caspase-1
View all literature mentionsThis polyclonal targets Mouse IL-1 beta / IL-1F2
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets RNA polymerase II CTD repeat YSPTSPS (phospho S5) antibody - ChIP Grade
View all literature mentionsThis polyclonal targets HDAC2 antibody - ChIP Grade
View all literature mentionsThis polyclonal targets IRF8
View all literature mentionsThis polyclonal targets PU.1 (Spi-1) (T-21)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets NLRP3/NALP3
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentionsThis polyclonal targets Mouse ECF-L / CHI3L3
View all literature mentionsThis monoclonal targets NLRP3/NALP3
View all literature mentionsThis polyclonal targets Mouse ECF-L / CHI3L3
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentionsThis polyclonal targets Mouse ECF-L / CHI3L3
View all literature mentionsThis monoclonal targets NLRP3/NALP3
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentionsThis polyclonal targets Mouse ECF-L / CHI3L3
View all literature mentionsThis monoclonal targets NLRP3/NALP3
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentions