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GSE23436
Mus musculus, Homo sapiens
6 Downloadable Samples
Illumina Genome Analyzer II
Description
Cell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Publication Title
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
We identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett''s esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts Overall design: [RNA-Seq] Total RNA isolated from CPA control cells and CPA cells following SOX15 depletion, samples were prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75 base pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype. [ChIP-Seq] Examine SOX15-chromatin binding in CPA cells.
Publication Title
SOX15 governs transcription in human stratified epithelia and a subset of esophageal adenocarcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt ligands signal in many mammalian tissues, including the intestinal epithelium, where constitutive signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted transcription factor CDX2 in colonic cells uncovered highly significant over-representation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling. Chromatin immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy of CDX2 and TCF4 across short distances. A region spanning the single nucleotide polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal cancer risk in humans, represented one of many co-occupied sites. Co-occupancy correlated with intestine-specific gene expression and CDX2 loss reduced TCF4 binding.These results implicate CDX2 in directing TCF4 binding in intestinal cells. Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes.
Publication Title
TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identifiy core GATA6 functions and transcriptional targets in human gastric cancer, including additional subservient transcriptional regulators via integrative analysis of GATA6 transcription factor occupancy, gene dependency, and tumor synexpression.
Publication Title
An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2500
Description
We performed a genome-scale CRISPR screen in a KRAS-mutant pancreatic cancer cell line treated with the MEK inhibitor trametinib, and found that loss of the transcriptional repressor CIC confers resistance to MEK inhibition. We determined that CIC loss also confers resistance to MEK or BRAF inhibition in lung cancer, colorectal cancer, and melanoma cell lines with mutant RAS or BRAF. CIC is a transcriptional repressor that is phosphorylated and inhibited by the MAPK pathway. We hypothesized that inhibition of the MAPK pathway would lead to activation of CIC and repression of CIC target genes. Loss of CIC would therefore restore expression of these genes, conferring drug resistance. To identify the relevant CIC target genes that mediate trametinib resistace, we generated 4 Cas9-expressing cell lines from different lineages and with different RAS or RAF mutations, and generated control (gGFP) or CIC-knockout (gCIC) cell lines. We treated cells with DMSO or trametinib for 24 hours, and performed NRA-seq. We found that trametinib treatment reduces expression of at least one member of the PEA3 family of ETS transcription factors (ETV1, ETV4, and ETV5) in all cell lines assessed, and that loss of CIC results in maintained expression of these genes despite MEK inhibition. We further validated that ETV1, 4, and 5 expression was necessary for resistance mediated by CIC loss; and that ETV1, 4, or 5 expression was sufficient to confer trametinib resistance. Overall design: 4 Cas9-expressing human cancer cell lines (A549, CALU1, HCT116, PATU8902) were used to generate 3 isogenic cell lines with intact CIC (gGFP-1) or knocked out CIC (gCIC-1 or gCIC-2). Each of these 12 cell lines were treated with DMSO or trametinib for 24 hours (duplicates)
Publication Title
ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. The goal of this study is to determine the function of and the genes regulated by Sox2 in the stomach. Methods: mRNA profiles of Sox2 WT and Sox2 KO gastric glands were generated by RNA-sequencing, in triplicate, using a Illumina HiSeq 2500 instrument, resulting in 36 million single-end 50bp reads per smaple. Sequencing reads were mapped to the mouse reference genome (mm10/GRCm38) using STAR (Dobin et al., 2013). Read counts over transcripts were calculated using HTSeq v.0.6.0 (Anders et al., 2015) based on a current Ensembl annotation file for mm10/GRCm38 (release 75). Results: Sox2 is dispensiable for gastric stem cell self-renewal and epithelial homeostasis, however modulates the expression of cancer and intestinal related genes. Overall design: mRNA profiles of stomachs from 10 week old Sox2 WT and Sox2 KO mice were generated by sequencing, in triplicate, using a Illumina HiSeq 2500.
Publication Title
Sox2 Suppresses Gastric Tumorigenesis in Mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Analysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 13 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Analysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
An antagonistic interplay between YAP and RUNX where RUNX proteins abrogate YAP-mediated transcription of EMT and Stemness associated genes in mammary epithelial cells in an interaction dependent manner.
Publication Title
RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer.
Sample Metadata Fields
Cell line
View Samples