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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 18, 2021 |
| Title |
High throughput screening identifies SOX2 as a Super Pioneer Factor that inhibits DNA methylation maintenance at its binding sites |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
Access of mammalian transcription factors (TFs) to regulatory regions, an essential event for transcription regulation, is hindered by chromatin compaction involving nucleosome wrapping, repressive histone modifications and DNA methylation. Moreover, methylation of TF binding sites (TBSs) affects TF binding affinity to these sites. Remarkably, a special class of TFs called pioneer transcription factors (PFs) can access nucleosomal DNA, leading to nucleosome remodelling and chromatin opening. However, whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown.
Here, we set up a highly parallelized approach to investigate PF ability to bind methylated DNA and induce demethylation. Our results indicate that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs that have a strong pioneering activity; while most PFs do not induce changes in DNA methylation at their binding sites, we identified PFs that can protect DNA from methylation and PFs that can induce DNA demethylation at methylated binding sites. We called the latter “super pioneer transcription factors” (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Importantly, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation by inhibition of the maintenance methyltransferase DNMT1 during replication. This important finding suggests a novel mechanism allowing TFs to interfere with the epigenetic memory during DNA replication.
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| Overall design |
RNA-seq – Bisulfite-Seq – AmpBis-Seq - Sanger
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| Contributor(s) |
Vanzan L, Soldati H, Ythier V, Anand S, Francis N, Braun S, Murr R |
| Citation(s) |
34099689 |
| Submission date |
Jan 30, 2020 |
| Last update date |
Jun 15, 2021 |
| Contact name |
victor YTHIER |
| E-mail(s) |
Victor.Ythier@unige.ch
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| Organization name |
University of Geneva
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| Department |
GEDEV
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| Street address |
Rue Michel-Servet,1
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| City |
Geneva |
| State/province |
Geneva |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (3) |
| GPL15907 |
AB 5500xl Genetic Analyzer (Mus musculus) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA603914 |
| SRA |
SRP246086 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144524_ESC_counts.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| GSE144524_ESC_untrt_merge_mincov0.tab.gz |
30.0 Kb |
(ftp)(http) |
TAB |
| GSE144524_ESC_untrt_pm_mincov10.tab.gz |
4.7 Kb |
(ftp)(http) |
TAB |
| GSE144524_NP_counts.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| GSE144524_NP_sssi_merge_mincov0.tab.gz |
38.8 Kb |
(ftp)(http) |
TAB |
| GSE144524_NP_sssi_pm_mincov10.tab.gz |
4.6 Kb |
(ftp)(http) |
TAB |
| GSE144524_RAW.tar |
110.0 Kb |
(http)(custom) |
TAR (of TAB) |
| GSE144524_TETTKO_counts.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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