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Series GSE119057 Query DataSets for GSE119057
Status Public on Aug 28, 2018
Title Genome-wide Estrogen Receptor-alpha activation time-course
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Estrogen Receptor-alpha (ER) is the key driver of 75% of all breast cancers. Upon stimulation by its ligand estra-2-diol, ER forms a transcriptionally active complex binding chromatin. Previous studies have reported that ER binding follows a cyclical binding pattern with a periodicity of 90 minutes. However, these studies have been limited to individual ER target genes and most were done without replicates. Thus, the robustness and generality of ER cycling are not well understood. Here we present a comprehensive genome-wide analysis of the time dependence of ER binding affinity up to 90 minutes after activation, based on 6 replicates at 10 time points using our previously reported method for precise quantification of binding, Parallel-Factor ChIP-seq (pfChIP-seq). In contrast to previously described cyclical binding, our approach identifies a unidirectional sustained increase in ER binding affinity, as well as a class of estra-2-diol independent binding sites. Our results are corroborated by a quantitative re-analysis of data from multiple independent studies. Our new model reconciles the results of multiple conflicting studies into the activation of ER at the TFF1 promoter. We provide a detailed understanding of ER's response to estra-2-diol in the context of the receptor's fundamental role as both the main driver and therapeutic target of breast cancer
Overall design 6 indepednant pfChip-seq replicates measuring ER binding at 10 timepoints between 0 to 90 minutes.
Contributor(s) Holding AN, Cullen AE, Markowetz F
Citation(s) 30457555
Submission date Aug 26, 2018
Last update date Mar 21, 2019
Contact name Andrew Nicholas Holding
Organization name University of Cambridge
Department CRUK Cambridge Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (59)
GSM3357114 ER t30 Rep 6 [t30.6]
GSM3357115 ER t60 Rep 1 [t60.1]
GSM3357116 ER t90 Rep 3 [t90.3]
BioProject PRJNA487952
SRA SRP158854

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE119057_SupplementaryTable1.csv.gz 3.2 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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