 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Mar 08, 2022 |
| Title |
Differential cofactor dependencies define functionally distinct types of human enhancers (PRO-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Development and homeostasis of all multicellular organisms rely on differential cell-type-specific gene expression that is regulated by non-coding genomic enhancer elements. Enhancers function through the transcription-factor-mediated recruitment of cofactors, a structurally and functionally diverse set of proteins that activate RNA polymerase II transcription at promoters. Despite the important roles of enhancers and cofactors in transcriptional regulation, it is still not clear if all cofactors are required for all enhancers or if different enhancers have distinct cofactor dependencies and whether differential cofactor dependencies could be used to functionally categorize enhancers. Here, we quantified enhancer activities along the entire human genome using the massively parallel enhancer-activity assay STARR-seq in HCT116 cells, following the rapid auxin-inducible degradation of eight different cofactors. We identified groups of enhancers with distinct cofactor requirements, including enhancers whose activity is insensitive to the depletion of the core Mediator subunit MED14 or the bromodomain protein BRD4, respectively. In particular, Mediator seemed dispensable for P53-responsive enhancers and MED14-depleted cells in which transcription globally failed were still able to induce endogenous P53 target genes such as p21. Similarly, BRD4 was not required for genes with a CCAAT- and TATA-box proximal enhancer, including histone genes and LTR12 family retrotransposons, and for the induction of TATA-box containing heat-shock genes. Taken together, we show that different types of enhancers with distinct cofactor dependencies exist, including enhancer types that function in the absence of well-known cofactors and are employed to regulate specific gene classes and transcriptional programs. This represents the first functional categorization of enhancers by their cofactor dependencies that improves our understanding of alternative ways to activate transcription, which can aid in developing more precise interventions to modulate gene expression.
|
| |
|
| Overall design |
Nascent RNA transcription measured by PRO-seq in WT, MED14- or BRD4-AID-tagged HCT116 cells, upon P53 induction by Nutlin-3a and/or respective COF depletion. Each COF-AID-tagged cell line was treated with auxin (IAA) to deplete the respective COF or water (mock) as a control. Each cell line was in addition treated with Nutlin-3a to induce P53 signaling on top of either auxin or mock treatment. For MED14-AID cell line, two different treatment regimens were performed: 1) 3h auxin/mock treatment followed by 3h Nutlin-3a treatment, or 2) 12h auxin/mock treatment followed by 6h Nutlin-3a treatment. All experiments were performed in 2 biological replicates.
|
| |
|
| Contributor(s) |
Neumayr C, Haberle V, Hendy O, Serebreni L, Arnold C, Bergauer K, Rath M, Pagani M, Stark A |
| Citation(s) |
35650434 |
| |
| Submission date |
Aug 24, 2020 |
| Last update date |
Jun 10, 2022 |
| Contact name |
Vanja Haberle |
| E-mail(s) |
[email protected]
|
| Organization name |
The Research Institute of Molecular Pathology (IMP)
|
| Lab |
Stark Lab
|
| Street address |
Campus-Vienna-Biocenter 1
|
| City |
Vienna |
| ZIP/Postal code |
1030 |
| Country |
Austria |
| |
|
| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL21697 |
NextSeq 550 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (32)
|
|
| This SubSeries is part of SuperSeries: |
| GSE156741 |
Differential cofactor dependencies define functionally distinct types of human enhancers |
|
| Relations |
| BioProject |
PRJNA658927 |
| SRA |
SRP278594 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156737_BRD4_0hrIAA_0hrNutlin.ns.bw |
342.0 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_0hrIAA_0hrNutlin.ps.bw |
353.7 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_0hrIAA_3hrNutlin.ns.bw |
356.6 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_0hrIAA_3hrNutlin.ps.bw |
368.7 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_3hrIAA_0hrNutlin.ns.bw |
226.7 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_3hrIAA_0hrNutlin.ps.bw |
232.3 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_3hrIAA_3hrNutlin.ns.bw |
201.2 Mb |
(ftp)(http) |
BW |
| GSE156737_BRD4_3hrIAA_3hrNutlin.ps.bw |
207.7 Mb |
(ftp)(http) |
BW |
| GSE156737_Brd4_3hrIAA_3hrNutlin_raw_counts_per_condition_for_promoter_and_genebody_regions.txt.gz |
933.4 Kb |
(ftp)(http) |
TXT |
| GSE156737_Brd4_raw_counts_per_condition_for_promoter_and_genebody_regions.txt.gz |
634.8 Kb |
(ftp)(http) |
TXT |
| GSE156737_Med14_0hrIAA_0hrNutlin.ns.bw |
503.6 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_0hrIAA_0hrNutlin.ps.bw |
522.7 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_0hrIAA_3hrNutlin.ns.bw |
458.8 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_0hrIAA_3hrNutlin.ps.bw |
475.6 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_3hrIAA_0hrNutlin.ns.bw |
307.0 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_3hrIAA_0hrNutlin.ps.bw |
320.1 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_3hrIAA_3hrNutlin.ns.bw |
390.0 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_3hrIAA_3hrNutlin.ps.bw |
406.9 Mb |
(ftp)(http) |
BW |
| GSE156737_Med14_3hrIAA_3hrNutlin_raw_counts_per_condition_for_promoter_and_genebody_regions.txt.gz |
975.3 Kb |
(ftp)(http) |
TXT |
| GSE156737_Med14_raw_counts_per_condition_for_promoter_and_genebody_regions.txt.gz |
817.5 Kb |
(ftp)(http) |
TXT |
| GSE156737_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BW) |
| GSE156737_WT_3hrNutlin.ns.bw |
124.8 Mb |
(ftp)(http) |
BW |
| GSE156737_WT_3hrNutlin.ps.bw |
128.4 Mb |
(ftp)(http) |
BW |
| GSE156737_WT_3hrNutlin_raw_counts_per_condition_for_promoter_and_genebody_regions.txt.gz |
686.3 Kb |
(ftp)(http) |
TXT |
| GSE156737_WT_DMSO.ns.bw |
106.2 Mb |
(ftp)(http) |
BW |
| GSE156737_WT_DMSO.ps.bw |
109.0 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...