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Series GSE144524 Query DataSets for GSE144524
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
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.
Overall design RNA-seq – Bisulfite-Seq – AmpBis-Seq - Sanger
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
Organization name University of Geneva
Department GEDEV
Street address Rue Michel-Servet,1
City Geneva
State/province Geneva
ZIP/Postal code 1211
Country Switzerland
Platforms (3)
GPL15907 AB 5500xl Genetic Analyzer (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (24)
GSM4290057 ESC rep1
GSM4290058 ESC rep2
GSM4290059 ESC rep3
BioProject PRJNA603914
SRA SRP246086

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE144524_ESC_counts.txt.gz 3.6 Mb (ftp)(http) TXT 30.0 Kb (ftp)(http) TAB 4.7 Kb (ftp)(http) TAB
GSE144524_NP_counts.txt.gz 3.6 Mb (ftp)(http) TXT 38.8 Kb (ftp)(http) TAB 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 SelectorHelp
Processed data are available on Series record
Raw data are available in SRA
Processed data provided as supplementary file

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