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Series GSE39435 Query DataSets for GSE39435
Status Public on Mar 27, 2014
Title Induced Cdx2 binding in embryonic stem cells and endodermal cells
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS’s multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions.
We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment.
Overall design In this study, we characterize the binding of Cdx2 in embryonic stem cells, endodermal cells, and progenitor motor neurons using V5- or FLAG-tagged doxycycline inducible Cdx2 ESC lines (iCdx2). Endoderm and progenitor motor neurons are generated from the ES cells using directed differentiation approaches. The cells are then exposed to Dox to express the tagged Cdx2 construct. The genome-wide binding of the induced full-length Cdx2 transcription factor is profiled using ChIP-seq with an anti-V5 or anti-FLAG antibody. We also examine the binding behavior of a truncated version of the Cdx2 protein, where a protein interaction domain contained in the first 59 amino acids has been deleted. An appropriate pseudo-IP control experiment for these ChIP-seq experiments has been previously submitted under accession number GSM766062.
Contributor(s) Mahony S, Mazzoni EO, Sherwood RI, Morrison CA, Gifford DK, Wichterle H
Citation(s) 24675637
Submission date Jul 17, 2012
Last update date May 15, 2019
Contact name Shaun Mahony
Phone 814-865-3008
Organization name Penn State University
Department Biochemistry & Molecular Biology
Lab Shaun Mahony
Street address 404 South Frear Bldg
City University Park
State/province PA
ZIP/Postal code 16802
Country USA
Platforms (1)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (5)
GSM968718 induced V5-tagged Cdx2 (iCdx2-V5) in embryonic stem cells [ChIP-seq]
GSM968719 induced FLAG-tagged truncated Cdx2 (iFLAG-Cdx2-truncated) in embryonic stem cells [ChIP-seq]
GSM982084 Pseudo-ChIP control using anti-V5 in progenitor motor neurons (Day_4 )
BioProject PRJNA170870
SRA SRP014446

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Supplementary file Size Download File type/resource
GSE39435_RAW.tar 2.2 Gb (http)(custom) TAR (of BAM, BW, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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