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SRP033057
Homo sapiens
2 Downloadable Samples
IlluminaHiSeq2000
Description
To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers'' putatively targeted genes, we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function Overall design: Two biological replicates of HCT116 were compared to the data of two normal colon samples already deposited in GEO (GSM1010974 and GSM1010942).
Publication Title
Functional annotation of colon cancer risk SNPs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We have analyzed publicly available K562 Hi-C data, which enables genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 46 transcription factors and 8 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into three types of chromatin hubs. The different clusters of loci display very different relationships with transcription factor binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 6, which is distinguished by marks of open chromatin but not by marks of active enhancers or promoters, was not bound by most transcription factors but was highly enriched for 3 transcription factors (GATA1, GATA2, and c-Jun) and 3 chromatin modifiers (BRG1, INI1, and SIRT6). To validate the identification of the clusters and to dissect the impact of chromatin organization on gene regulation, we performed RNA-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors greatly alters the expression of genes within cluster 6. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provide genome-wide evidence that Hi-C data identifies sets of biologically relevant interacting loci. Overall design: RNA-seq of control, siGATA1 and siGATA2 K562 cells
Publication Title
Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance Overall design: Differential RNA-seq profiling from triplicate biological replicates of MCF7 cells treated with scrambled siRNA or siZNF217.
Publication Title
Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
The TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in 6 human cell lines. We identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to the 6 cell lines. Using ChIP-seq, we showed that many genomic regions that are marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer activity. Bioinformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells. Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the genome via GATA3. Our studies demonstrate a novel relationship between GATA3 and TCF7L2, and reveal important insights into TCF7L2-mediated gene regulation. Overall design: RNAseq analysis of MCF7 cells transfected with siCONTROL, siTCF7L2 or siGATA3. ChIP-seq analysis of H3K27ac, H3K4me1, H3K27me3, H3K9me3 in MCF7 cells; H3K4me1 and H3K27ac in HCT116 cells.
Publication Title
Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis.
Publication Title
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
Total RNA was analyzed from either uninduced or -estradiol treated G1E-ER-GATA cells to determine changes in gene expression upon induction of erythroid maturation (treated).
Publication Title
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
We have compared the genome-wide effects on the transcriptome after treatment with ICG-001 (the specific CBP inhibitor) versus C646, a compound that competes with acetyl-coA for the Lys-coA binding pocket of both CBP and p300. We found that both drugs cause large-scale changes in the transcriptome of HCT116 colon cancer cells and PANC1 pancreatic cancer cells, and reverse some tumor-specific changes in gene expression. Interestingly, although the epigenetic inhibitors affect cell cycle pathways in both the colon and pancreatic cancer cell lines, the WNT signaling pathway was affected only in the colon cancer cells. Notably, WNT target genes were similarly down-regulated after treatment of HCT116 with C646 as with ICG-001. Overall design: To identify genes affected by direct targeting of a component of the transcriptional complex implicated in WNT regulation, we used siRNAs to knockdown TCF7L2 in PANC1 cells. Cells were treated with control siRNAs or siRNAs specific for TCF7L2 and RNA was analyzed by RNA-seq.
Publication Title
Three-dimensional analysis reveals altered chromatin interaction by enhancer inhibitors harbors TCF7L2-regulated cancer gene signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors. Overall design: Ikaros RNA-Seq from double positive thymocytes comparing wt (n=2), Ikaros-ZnF1-/- mutant (n=2) and Ikaros-ZnF4-/- mutant (n=2)
Publication Title
Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors. Overall design: RNA-Seq from sorted primary proB cell Hardy Fractions B and C+C'', comparing wt, Ikaros-ZnF1-/- mutant and Ikaros-ZnF4-/- mutant.
Publication Title
Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 97 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The NIH Roadmap Epigenomics Mapping Consortium aims to produce a public resource of epigenomic maps for stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease.
Publication Title
The NIH Roadmap Epigenomics Mapping Consortium.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples