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Series GSE31939 Query DataSets for GSE31939
Status Public on Nov 22, 2011
Title VDR/RXR and TCF4/beta-Catenin Cistromes in Colonic Cells of Colorectal Tumor Origin: Impact on c-FOS and c-MYC Gene Expression
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by array
Summary Many of the transcriptional and growth regulating activities of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the intestine and colon are recapitulated in the human colorectal cancer cell LS180. We therefore used this line together with ChIP-seq and gene expression analyses to identify the vitamin D receptor (VDR)/retinoid x receptor (RXR) and TCF7L2(TCF4)/β-catenin cistromes and the genes that they regulate. VDR and RXR co-localized to predominantly promoter distal, VDRE-containing sites in a largely ligand-dependent manner. These regulatory sites control the expression of both known as well as novel 1,25(OH)2D3 target genes. TCF4 and β-catenin cistromes partially overlapped, contained TCF/LEF consensus elements, and were only modestly influenced by 1,25(OH)2D3. However, the two heterodimer complexes co-localized at sites near a limited set of genes that included c-FOS and c-MYC; the expression of both genes was modulated by 1,25(OH)2D3. At the c-FOS gene, both VDR/RXR and TCF4/β-catenin bound to a single distal enhancer located 24 kb upstream of the transcriptional start site. At the c-MYC locus, however, binding was noted at a cluster of sites between -139 and -165 kb and at a site located -335 kb upstream. Examined as isolated enhancer fragments, these regions exhibited basal and 1,25(OH)2D3-inducible activities that were interlinked to both VDR and β-catenin activation. These data reveal additional complexity in the regulation of target genes by 1,25(OH)2D3 and support a direct action of both VDR and the TCF4/β-catenin regulatory complex at c-FOS and c-MYC.
Overall design 13 samples are analyzed by ChIP-seq. The Input was used as the normalizing factor for all transcription factor IPs. A minimum of 2 replicates were run per antibody and condition. After analysis, these lanes were combined for greater read depth. RNA was isolated from biological replicate experiments for a total of 6 samples in this study (3x 0hr, 3x 24hr), reverse transcribed and labeled according to Nimblegen Systems, Inc. (Madison, WI) protocols.
Web link
Contributor(s) Meyer MB, Goetsch PD, Pike JW
Citation(s) 22108803
Submission date Sep 06, 2011
Last update date May 15, 2019
Contact name Mark B Meyer
Phone 608-890-0857
Organization name University of Wisconsin-Madison
Department Nutritional Sciences
Lab Meyer Lab
Street address 1415 Linden Dr.
City Madison
State/province WI
ZIP/Postal code 53706
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11219 NimbleGen Homo sapiens HG18 60mer expr (385k)
Samples (19)
GSM791403 LS180_VDR_Veh
GSM791404 LS180_VDR_125
GSM791405 LS180_RXR_Veh
SRA SRP008120
BioProject PRJNA145015

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

Supplementary file Size Download File type/resource
GSE31939_RAW.tar 23.9 Gb (http)(custom) TAR (of BED, CALLS, PAIR, TIFF, TXT)
GSE31939_antibody_details_ChIP_methods.txt.gz 3.2 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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