Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The Nuclear Receptor PPARγ Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory.

Bence Daniel | Gergely Nagy | Zsolt Czimmerer | Attila Horvath | David W Hammers | Ixchelt Cuaranta-Monroy | Szilard Poliska | Petros Tzerpos | Zsuzsanna Kolostyak | Tristan T Hays | Andreas Patsalos | René Houtman | Sascha Sauer | Jean Francois-Deleuze | Fraydoon Rastinejad | Balint L Balint | H Lee Sweeney | Laszlo Nagy
Immunity | 2018

Macrophages polarize into distinct phenotypes in response to complex environmental cues. We found that the nuclear receptor PPARγ drove robust phenotypic changes in macrophages upon repeated stimulation with interleukin (IL)-4. The functions of PPARγ on macrophage polarization in this setting were independent of ligand binding. Ligand-insensitive PPARγ bound DNA and recruited the coactivator P300 and the architectural protein RAD21. This established a permissive chromatin environment that conferred transcriptional memory by facilitating the binding of the transcriptional regulator STAT6 and RNA polymerase II, leading to robust production of enhancer and mRNAs upon IL-4 re-stimulation. Ligand-insensitive PPARγ binding controlled the expression of an extracellular matrix remodeling-related gene network in macrophages. Expression of these genes increased during muscle regeneration in a mouse model of injury, and this increase coincided with the detection of IL-4 and PPARγ in the affected tissue. Thus, a predominantly ligand-insensitive PPARγ:RXR cistrome regulates progressive and/or reinforcing macrophage polarization.

Pubmed ID: 30332629

Additional research tools detected in this publication

Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 210664/Z/18/Z
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK115924
  • Agency: NIAMS NIH HHS, United States
    Id: U54 AR052646

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.

This is a list of tools and resources that we have found mentioned in this publication.


Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

View all literature mentions

PeproTech (tool)

RRID:SCR_006802

An Antibody supplier

View all literature mentions

SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

View all literature mentions

PPARγ (81B8) Rabbit mAb (antibody)

RRID:AB_823598

This monoclonal targets PPARgamma

View all literature mentions

GAPDH (6C5) (antibody)

RRID:AB_627679

This monoclonal targets GAPDH (6C5)

View all literature mentions

POLR2AphosphoS2-human (antibody)

RRID:AB_304749

This polyclonal targets POLR2AphosphoS2

View all literature mentions

RXR (??N 197) (antibody)

RRID:AB_2270041

This polyclonal targets RXR (??N 197)

View all literature mentions

Purified anti-mouse Ly-6G (antibody)

RRID:AB_1089179

This monoclonal targets Ly-6G

View all literature mentions

IL4 antibody (antibody)

RRID:AB_308768

This polyclonal targets IL4 antibody

View all literature mentions

Stat6 (M-20) (antibody)

RRID:AB_632450

This polyclonal targets STAT6

View all literature mentions

H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

View all literature mentions

EP300-human (antibody)

RRID:AB_2231120

This unknown targets EP300

View all literature mentions

Rabbit Anti-SRC1 Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_303360

This polyclonal targets KAT13A / SRC1 - ChIP Grade

View all literature mentions

RXRA-human (antibody)

RRID:AB_2184874

This polyclonal targets RXRA

View all literature mentions

Ingenuity Pathway Analysis (pathway analysis tool)

RRID:SCR_008653

A web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.

View all literature mentions

DiffBind (software resource)

RRID:SCR_012918

Compute differentially bound sites from multiple ChIP-seq experiments using affinity (quantitative) data. Also enables occupancy (overlap) analysis and plotting functions.

View all literature mentions

Cufflinks (software resource)

RRID:SCR_014597

Software 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 mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical 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 mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

BEDTools (software resource)

RRID:SCR_006646

A 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 mentions

TopHat (software resource)

RRID:SCR_013035

Software 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 mentions

TreeView (software resource)

RRID:SCR_013503

Software to graphically browse results of clustering and other analyses from Cluster.

View all literature mentions

ngs.plot (software resource)

RRID:SCR_011795

A software program that allows you to easily visualize your next-generation sequencing (NGS) samples at functional genomic regions.

View all literature mentions

HOMER (software resource)

RRID:SCR_010881

Software 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 mentions

IL4 antibody (antibody)

RRID:AB_308768

This polyclonal targets IL4 antibody

View all literature mentions

BWA (software resource)

RRID:SCR_010910

Software 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 mentions

Bamtools (software resource)

RRID:SCR_015987

Software that provides both a C++ API and a command-line toolkit for reading, writing, and manipulating genome sequence alignment files in the BAM and SAM formats. It is used for research analysis and management of data produced by sequencing technologies.

View all literature mentions

Integrative Genomics Viewer (software resource)

RRID:SCR_011793

A high-performance visualization tool for interactive exploration of large, integrated genomic datasets.

View all literature mentions

MACS (software resource)

RRID:SCR_013291

Software Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.

View all literature mentions

DAVID (software resource)

RRID:SCR_001881

Bioinformatics 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 mentions

SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

View all literature mentions