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Series GSE45914 Query DataSets for GSE45914
Status Public on Jun 05, 2013
Title Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Rev-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.
Overall design Using ChIPseq, GRO-seq, and 5'GRO-seq to determine mechanism of RevErb in transcriptional regulation in macrophages
Contributor(s) Lam MT, Cho H, Lesch HP, Gosselin D, Heinz S, Tanaka-Oishi Y, Benner C, Kaikkonen MU, Kim AS, Kosaka M, Lee CY, Watt A, Grossman TR, Rosenfeld MG, Evans RM, Glass CK
Citation(s) 23728303
Submission date Apr 09, 2013
Last update date May 15, 2019
Contact name Michael T Lam
Organization name University of California, San Diego
Department School of Medicine
Lab Christopher Glass
Street address 9500 Gilman Drive, MC 0651
City La Jolla
State/province CA
ZIP/Postal code 92093
Country USA
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (15)
GSM1119594 BirA, biotin ChIPseq
GSM1119595 BLRP-RevErbalpha, biotin ChIPseq
GSM1119596 BLRP-RevErbbeta, biotin ChIPseq
BioProject PRJNA196871
SRA SRP021025

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Supplementary file Size Download File type/resource
GSE45914_RAW.tar 324.2 Mb (http)(custom) TAR (of BEDGRAPH)
GSE45914_RevErb_common_H3K4m1_H3K4m3lo_intergenic.txt.gz 8.9 Kb (ftp)(http) TXT
GSE45914_RevErb_common_H3K4m1hi_H3K4m3lo.txt.gz 20.3 Kb (ftp)(http) TXT
GSE45914_RevErb_common_peaks.txt.gz 25.1 Kb (ftp)(http) TXT
GSE45914_RevErb_peaks_summary.txt.gz 118.4 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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