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| 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
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| 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.
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| 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.
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| Web link |
http://genome.ucsc.edu/cgi-bin/hgTracks?hgS_doOtherUser=submit&hgS_otherUserName=Pike%20Lab%20Data&hgS_otherUserSessionName=GSE31939_data
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| Contributor(s) |
Meyer MB, Goetsch PD, Pike JW |
| Citation(s) |
22108803 |
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| Submission date |
Sep 06, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Mark B Meyer |
| E-mail(s) |
markmeyer@wisc.edu
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| Phone |
608-890-0857
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| Organization name |
University of Wisconsin-Madison
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| Department |
Nutritional Sciences
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| Lab |
Meyer Lab
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| Street address |
1415 Linden Dr.
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53706 |
| Country |
USA |
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| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11219 |
NimbleGen Homo sapiens HG18 60mer expr (385k) |
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| Samples (19)
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| Relations |
| SRA |
SRP008120 |
| BioProject |
PRJNA145015 |
| 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 Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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