Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
AccessionGSE45914
TitleRev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription
DescriptionRev-Erba and Rev-Erbb are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm, metabolism, and inflammatory responses. Rev-Erbs function as transcriptional repressors by recruiting NCoR/HDAC3 co-repressor complexes to Rev-Erb response elements in enhancers and promoters of target genes, but the molecular basis for cell-specific programs of repression is not known. Here, we present evidence that in macrophages, Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby mRNAs, implying a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a method that quantifies nascent 5' ends (5'-GRO-Seq), we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for direct roles of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45914
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Canned Analyses generated with the dataset

Dataset Accession
Tool Name

Interactive heatmap visualization of RNA-seq dataset GSE45914
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.