Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Daniel B

PROVIDER: S-EPMC6197058 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-06-20 | GSE115505 | GEO

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [RNA-Seq2]

Project description:Macrophages change their phenotype in response to complex (reinforcing or opposing) environmental cues. The molecular components providing the epigenomic basis of progressive or reinforcing polarization are largely unknown. Here we show that the normally ligand-activated nuclear receptor, Peroxisome Proliferator-Activated Receptor gamma (PPARγ), is a predominantly ligand-insensitive, epigenomic driver of a robust phenotypic change in macrophages uniquely upon repeated/reinforcing IL-4 stimulation. Ligand-insensitive PPARγ recruits P300, RAD21 and establishes a permissive chromatin environment, conferring transcriptional memory by facilitating the binding of STAT6 and RNAPII leading to more robust eRNA production upon IL-4 restimulation. PPARγ-mediated transcriptional memory allows the progressive, functional transition of macrophages upon repeated cytokine exposure by controlling the expression of an extracellular matrix remodeling related gene network, also expressed in macrophages from a mouse model of muscle regeneration and show progressive upregulation during the course of regeneration after muscle injury, coinciding with the appearance of IL-4 and PPARγ. Collectively, in contrast to the current prevailing view, alternative polarization gives rise to a predominantly ligand-insensitive PPARγ:RXR cistrome, regulating progressive/reinforcing macrophage polarization.

2018-06-20 | GSE115504 | GEO

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [RNA-Seq]

2018-06-20 | GSE115502 | GEO

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [ATAC-seq]

2018-06-20 | GSE115085 | GEO

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [ChIP-seq]

2018-06-20 | GSE115083 | GEO

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory

Project description:Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory

| PRJNA476688 | ENA

Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [RNA-Seq]

Project description:Ligand-insensitive PPARγ controls progressive or reinforcing macrophage polarization as an epigenomic ratchet of transcriptional memory [RNA-Seq]

| PRJNA476691 | ENA

Sema6D reverse signaling controls lipid metabolism for macrophage polarization linking mTOR to PPARγ

Project description:Purpose: The goal of this study is to compare downstream genes of Sema6D signaling in LPS plus IFNg stimulated macrophages. Methods: Bone marrow derived macrophage mRNA profiles of 7 weeks of wild type (WT) and Sema6D-/- mice were stimulated by LPS for 4 hrs. Results: According to this comparison, we found that 550 genes were downregulated in Sema6D-/- macrophages than WT macrophages in response to LPS. Conclusions: Our study represents 62 genes were supressed in both M1 and M2 Sema6D-/- macrophage than WT macrophages, suggesting of Sema6D reverse sigaling genes.

2018-05-20 | GSE99047 | GEO

Sema6D reverse signaling controls lipid metabolism for macrophage polarization linking mTOR to PPARγ

Project description:The goal of this study is to compare downstream genes of Sema6D signaling in both M1 and M2 macrophages.

2018-05-20 | GSE99046 | GEO

Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.

Project description: Not available

| S-EPMC5524187 | biostudies-literature