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| 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
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| 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.
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| Overall design |
Using ChIPseq, GRO-seq, and 5'GRO-seq to determine mechanism of RevErb in transcriptional regulation in macrophages
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| 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 |
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| Submission date |
Apr 09, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Michael T Lam |
| E-mail(s) |
mtlam@ucsd.edu
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| Organization name |
University of California, San Diego
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| Department |
School of Medicine
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| Lab |
Christopher Glass
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| Street address |
9500 Gilman Drive, MC 0651
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (15)
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| GSM1119597 |
RevErb WT BMDM, GRO-seq |
| GSM1119598 |
RevErb DKO BMDM, GRO-seq |
| GSM1119599 |
BTEV-Ctrl, 5'GRO-seq |
| GSM1119600 |
BLRP-RevErba, 5'GRO-seq |
| GSM1119601 |
RevErb WT BMDM, H3K9ac ChIPseq |
| GSM1119602 |
RevErb DKO BMDM, H3K9ac ChIPseq |
| GSM1119603 |
BTEV-Ctrl, H3K9ac ChIPseq |
| GSM1119604 |
BLRP-RevErba, H3K9ac ChIPseq |
| GSM1119605 |
BTEV-Ctrl, H3K4me1 ChIPseq |
| GSM1119606 |
BLRP-RevErba, H3K4me1 ChIPseq |
| GSM1119607 |
BTEV-Ctrl, PU.1 ChIPseq |
| GSM1119608 |
BLRP-RevErba, PU.1 ChIPseq |
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| Relations |
| BioProject |
PRJNA196871 |
| SRA |
SRP021025 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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