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| Status |
Public on Jan 20, 2019 |
| Title |
CG dinucleotides enhance promoter activity independent of DNA methylation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Other
|
| Summary |
Most mammalian RNA Polymerase II initiation events occur at CpG islands, which are rich in CpGs and devoid of DNA methylation. Despite their relevance for gene regulation, it is unknown to what extent the CpG dinucleotide itself actually contributes to promoter activity. To address this question, we determined the transcriptional activity of a large number of chromosomally integrated promoter constructs and monitored binding of transcription factors assumed to play a role in CpG island activity. This revealed that CpG density significantly improves motif-based prediction of transcription factor binding. Our experiments also show that high CpG density alone is insufficient for transcriptional activity, yet results in increased transcriptional output when combined with particular transcription factor motifs. Yet, this CpG contribution to promoter activity is independent of DNA methyltransferase activity. Together this refines our understanding of mammalian promoter regulation as it shows that high CpG density within CpG islands directly contributes to an environment permissive for full transcriptional activity.
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| Overall design |
We monitored binding of transcription factors assumed to play a role in CpG island activity using ChIPseq and tested expression of a large number of promoter mutants, including artificial promoter sequences, when inserted into the genome using a novel high throughput transcriptional reporter assay.
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| Contributor(s) |
Hartl D, Krebs AR, Grand RS, Baubec T, Isbel L, Wirbelauer C, Burger L, Schübeler D |
| Citation(s) |
30709850 |
| Submission date |
Jul 06, 2018 |
| Last update date |
Apr 08, 2019 |
| Contact name |
Dirk Schuebeler |
| Organization name |
Friedrich Miescher Institute for Biomedical Research
|
| Street address |
Maulbeerstrasse 66
|
| City |
Basel |
| ZIP/Postal code |
4058 |
| Country |
Switzerland |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (186)
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| Relations |
| BioProject |
PRJNA479961 |
| SRA |
SRP152497 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116704_CpGDensitylib1_results.tab.gz |
3.2 Kb |
(ftp)(http) |
TAB |
| GSE116704_HKG_methylation.tab.gz |
881 b |
(ftp)(http) |
TAB |
| GSE116704_HKGlib1_results.tab.gz |
459 b |
(ftp)(http) |
TAB |
| GSE116704_HKGlib2_results.tab.gz |
10.7 Kb |
(ftp)(http) |
TAB |
| GSE116704_HKGlib3_results.tab.gz |
7.8 Kb |
(ftp)(http) |
TAB |
| GSE116704_RAW.tar |
116.7 Mb |
(http)(custom) |
TAR (of WIG) |
| GSE116704_Snx3Lib1_results.tab.gz |
5.2 Kb |
(ftp)(http) |
TAB |
| GSE116704_pwp2_lib3_results.tab.gz |
4.8 Kb |
(ftp)(http) |
TAB |
| GSE116704_pwp2_lib4_results.tab.gz |
2.9 Kb |
(ftp)(http) |
TAB |
| GSE116704_pwp2_lib5_results.tab.gz |
3.2 Kb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
| Raw data are available in SRA |
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