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| Status |
Public on Jul 14, 2023 |
| Title |
Widespread regulatory specificities between transcriptional corepressors and enhancers in Drosophila |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Animal development and homeostasis critically depend on the accurate regulation of gene expression, which includes the silencing of genes that should not be active. Silencing or repression of transcription is mediated by a specific class of transcription factors termed repressors that, typically via the recruitment of co-repressors (CoRs), can dominantly suppress transcription, even in the presence of activating cues. Here, we used functional genomics to discover previously unknown regulatory specificities between CoRs and enhancers. Enhancers can typically be repressed by only a subset of CoRs. Enhancers classified by CoR sensitivity also show distinct biological functions and endogenous chromatin features. Moreover, enhancers that are sensitive or resistant to silencing by specific CoRs differ in TF motif content. Strikingly, we identified TF motifs that are necessary and sufficient for resistance to specific CoRs, and can predict enhancer sensitivity to CoRs based on TF motif content.
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| Overall design |
We evaluted the direct effect of 5 CoRepressors on the activity of enhancers in Drosophila S2 cells using a modified version of STARR-seq termed repressor-STARR-seq. The repressors CoRest, CtBP, Rbf, Rbf2 and Sin3A are fused to the Gal4-DNA-binding domain and recruited next to the enhancer library through 4xUAS sites. Additionally we also tested the effect of recruiting CtBP and Rbf upstream of the promoter or upstream of the enhancers. We performed genome-wide and BAC screens (~750bp) and desigend oligonucleotide (250bp) screens, each sample with biological replicate. Reads were internally normalized, using a spike-in control of D. Pseudoobscura enhancers, lacking the 4xUAS binding sites.
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| Web link |
http://DOI: 10.1126/science.adf6149
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| Contributor(s) |
Jacobs J, Pagani M, Wenzl C, Stark A |
| Citation(s) |
37440660 |
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| Submission date |
Oct 10, 2022 |
| Last update date |
Oct 13, 2023 |
| Contact name |
Jelle Jacobs |
| E-mail(s) |
jelle.jacobs9255@gmail.com
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| Organization name |
Institute of molecular Pathology
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| Department |
VBC
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| Lab |
Stark lab
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| Street address |
Campus-Vienna-Biocenter 1
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| City |
Vienna |
| ZIP/Postal code |
1030 |
| Country |
Austria |
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| Platforms (3) |
| GPL22106 |
NextSeq 550 (Drosophila melanogaster) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
| GPL30203 |
NextSeq 2000 (Drosophila melanogaster) |
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| Samples (60)
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| GSM6623164 |
repSTARR-seq, CoRest, rep2 |
| GSM6623165 |
repSTARR-seq, CtBP, rep1 |
| GSM6623166 |
repSTARR-seq, CtBP, rep2 |
| GSM6623167 |
repSTARR-seq, Rbf, rep1 |
| GSM6623168 |
repSTARR-seq, Rbf, rep2 |
| GSM6623169 |
repSTARR-seq, Rbf2, rep1 |
| GSM6623170 |
repSTARR-seq, Rbf2, rep2 |
| GSM6623171 |
repSTARR-seq, Sin3A, rep1 |
| GSM6623173 |
repSTARR-seq, Sin3A, rep2 |
| GSM6623174 |
input, enhancers, repSTARR-seq, gw,DSCP |
| GSM6623175 |
input, enhancers, repSTARR-seq, gw,Rps12 |
| GSM6623176 |
olig-repSTARR-seq, DSCP, GFP, rep1 |
| GSM6623177 |
olig-repSTARR-seq, DSCP, GFP, rep2 |
| GSM6623178 |
olig-repSTARR-seq, DSCP, CoRest, rep1 |
| GSM6623179 |
olig-repSTARR-seq, DSCP, CoRest, rep2 |
| GSM6623180 |
olig-repSTARR-seq, DSCP, CtBP, rep1 |
| GSM6623181 |
olig-repSTARR-seq, DSCP, CtBP, rep2 |
| GSM6623182 |
olig-repSTARR-seq, DSCP, Rbf, rep1 |
| GSM6623183 |
olig-repSTARR-seq, DSCP, Rbf, rep2 |
| GSM6623184 |
olig-repSTARR-seq, DSCP, Rbf2, rep1 |
| GSM6623185 |
olig-repSTARR-seq, DSCP, Rbf2, rep2 |
| GSM6623187 |
olig-repSTARR-seq, DSCP, Sin3A, rep1 |
| GSM6623188 |
olig-repSTARR-seq, DSCP, Sin3A, rep2 |
| GSM6623189 |
olig-repSTARR-seq, Rps12, GFP, rep1 |
| GSM6623190 |
olig-repSTARR-seq, Rps12, GFP, rep2 |
| GSM6623191 |
olig-repSTARR-seq, Rps12, CoRest, rep1 |
| GSM6623192 |
olig-repSTARR-seq, Rps12, CoRest, rep2 |
| GSM6623193 |
olig-repSTARR-seq, Rps12, CtBP, rep1 |
| GSM6623194 |
olig-repSTARR-seq, Rps12, CtBP, rep2 |
| GSM6623195 |
olig-repSTARR-seq, Rps12, Rbf, rep1 |
| GSM6623196 |
olig-repSTARR-seq, Rps12, Rbf, rep2 |
| GSM6623197 |
olig-repSTARR-seq, Rps12, Rbf2, rep1 |
| GSM6623198 |
olig-repSTARR-seq, Rps12, Rbf2, rep2 |
| GSM6623199 |
olig-repSTARR-seq, Rps12, Sin3A, rep1 |
| GSM6623201 |
olig-repSTARR-seq, Rps12, Sin3A, rep2 |
| GSM6623202 |
input,enhancers, olig-repSTARR-seq, DSCP, rep1 |
| GSM6623203 |
input,enhancers, olig-repSTARR-seq, DSCP, rep2 |
| GSM6623204 |
input,enhancers, olig-repSTARR-seq, Rps12, rep1 |
| GSM6623205 |
input,enhancers, olig-repSTARR-seq,Rps12, rep2 |
| GSM7295702 |
DE_UAS_STARR-seq, GFP, rep1 |
| GSM7295703 |
DE_UAS_STARR-seq, GFP, rep2 |
| GSM7295704 |
DE_UAS_STARR-seq, GFP, rep3 |
| GSM7295705 |
DE_UAS_STARR-seq, CtBP, rep1 |
| GSM7295706 |
DE_UAS_STARR-seq, CtBP, rep2 |
| GSM7295707 |
DE_UAS_STARR-seq, Rbf, rep1 |
| GSM7295708 |
DE_UAS_STARR-seq, Rbf, rep2 |
| GSM7295709 |
UE_UAS_STARR-seq, GFP, rep1 |
| GSM7295710 |
UE_UAS_STARR-seq, GFP, rep2 |
| GSM7295711 |
UE_UAS_STARR-seq, CtBP, rep1 |
| GSM7295712 |
UE_UAS_STARR-seq, CtBP, rep2 |
| GSM7295713 |
UE_UAS_STARR-seq, Rbf, rep1 |
| GSM7295714 |
UE_UAS_STARR-seq, Rbf, rep2 |
| GSM7295715 |
UP_UAS_STARR-seq, GFP, rep1 |
| GSM7295716 |
UP_UAS_STARR-seq, GFP, rep2 |
| GSM7295717 |
UP_UAS_STARR-seq, CtBP, rep1 |
| GSM7295718 |
UP_UAS_STARR-seq, CtBP, rep2 |
| GSM7295719 |
UP_UAS_STARR-seq, Rbf, rep1 |
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| Relations |
| BioProject |
PRJNA888990 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE215143_RAW.tar |
446.1 Mb |
(http)(custom) |
TAR (of BW) |
| GSE215143_normalized_counts_BAC_screens.tsv.gz |
26.8 Kb |
(ftp)(http) |
TSV |
| GSE215143_olig_repSTARR_seq_DSCP_raw_and_norm_counts.tsv.gz |
2.5 Mb |
(ftp)(http) |
TSV |
| GSE215143_olig_repSTARR_seq_Rps12_raw_and_norm_counts.tsv.gz |
2.5 Mb |
(ftp)(http) |
TSV |
| GSE215143_spike-in.normalized.reads.over.gw.enhancers.txt.gz |
216.1 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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