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Series GSE80808 Query DataSets for GSE80808
Status Public on Jun 08, 2016
Title Nucleation of DNA Repair Factors by FOXA1 Links DNA Demethylation to Transcriptional Pioneering
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary We report that the winged helix transcription factor FOXA1 is unexpectedly associated with components of single and double stranded-DNA repair complexes. Biochemical studies and high-throughput approaches validated the hierarchical composition of this FOXA1-nucleated machinery and revealed the dependency on FOXA1 for global targeting of the key repair polymerase POLB. Genome-wide DNA methylomes at single-base resolution demonstrated that FOXA1-DNA repair complex is functionally linked to DNA demethylation in a lineage specific fashion. Loss-of-function studies indicate that a significant portion of FOXA1-bound regions display localized reestablishment of methylation and that the subsets with most consistent hypermethylation are represented by active promoters and enhancers that also exhibit the greatest depletion of POLB following FOXA1 removal. Consistently, forced expression of FOXA1 commits its binding sites to an active DNA demethylation in a POLB dependent manner. Finally, we showed that FOXA1-associated DNA demethylation is tightly coupled with genomic targeting of estrogen receptor and estrogen responsiveness. Together, our results link FOXA1-associated DNA demethylation to its transcriptional pioneering.
 
Overall design Genome-wide FOXA1 and POLB binding were examined through ChIP-seq in MCF-7 cells. Whole-genome bisulfite sequencing was performed in replicates in siNS- or siFOXA1-transfected MCF-7 cells.
 
Contributor(s) Shang Y, Zhang Y
Citation(s) 27500525
Submission date Apr 29, 2016
Last update date May 15, 2019
Contact name Yu Zhang
Organization name Peking University Health Science Center
Street address Xueyuan Road
City Beijing
ZIP/Postal code 100191
Country China
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (8)
GSM2137769 FOXA1 ChIP-seq
GSM2137770 POLB ChIP-seq
GSM2137771 POLB/siFOXA1 ChIP-seq
Relations
BioProject PRJNA320049
SRA SRP074177

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
GSE80808_RAW.tar 2.5 Gb (http)(custom) TAR (of BEDGRAPH, TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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