Genome-wide maps of XBP1 binding sites in different breast cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Liu Xiaole
PROVIDER: S-ECPF-GEOD-49955 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-09-26 | GSE49955 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-09-26 | E-GEOD-49955 | biostudies-arrayexpress
Project description:We report the application of ChIP-seq, which combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing, to map genome-wide XBP1 binding sites in different breast cancer cell lines. We showed that HIF1α motif was enriched in XBP1 binding sites in triple negative breast cancer (TNBC) cell lines, but not enriched in ER positive breast cancer cell line. We also demonstrated that different breast cancer cell lines of the same sub-type had similar XBP1 binding sites, whereas different breast cancer sub-types had majorly different XBP1 binding sites. Finally, a model was applied to integrate XBP1 ChIP-seq data with expression data to predict XBP1's direct targets in TNBC cell line; the predicted direct targets were shown to be predictive of patient survival, and the prediction power was specific to TNBC patients. The above evidence indicates that XBP1 performs important functions in TNBC by interacting with HIF1α, and such regulation mechanism is specific to TNBC, which is later proved by follow-up experiments.This study represents the first detailed anaysis of XBP1 binding sites in different breast cancer cell lines.
2013-09-26 | GSE49952 | GEO
Project description:We report the application of ChIP-seq, which combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing, to map genome-wide XBP1 binding sites in different breast cancer cell lines. We showed that HIF1M-NM-1 motif was enriched in XBP1 binding sites in triple negative breast cancer (TNBC) cell lines, but not enriched in ER positive breast cancer cell line. We also demonstrated that different breast cancer cell lines of the same sub-type had similar XBP1 binding sites, whereas different breast cancer sub-types had majorly different XBP1 binding sites. Finally, a model was applied to integrate XBP1 ChIP-seq data with expression data to predict XBP1's direct targets in TNBC cell line; the predicted direct targets were shown to be predictive of patient survival, and the prediction power was specific to TNBC patients. The above evidence indicates that XBP1 performs important functions in TNBC by interacting with HIF1M-NM-1, and such regulation mechanism is specific to TNBC, which is later proved by follow-up experiments.This study represents the first detailed anaysis of XBP1 binding sites in different breast cancer cell lines. Examination of XBP1 binding sites in 2 cell types (3 cell lines).
2013-09-26 | E-GEOD-49952 | biostudies-arrayexpress
Project description:We report high-throughput profiling of TRIM25 binding sites in triple negative breast cancer cells.
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Project description:We have developed a method for mapping unmethylated sites in the human genome based on the resistance of TspRI-digested ends to ExoIII nuclease degradation. Digestion with TspRI and methylation-sensitive restriction endonuclease HpaII, followed by ExoIII and single-strand DNA nuclease allowed removal of DNA fragments containing unmethylated HpaII sites. We then used array comparative genomic hybridization (CGH) to map the sequences depleted by these procedures in human genomes derived from five human tissues, a primary breast tumor, and two breast tumor cell lines. Analysis of methylation patterns of the normal tissue genomes indicates that the hypomethylated sites are enriched in the 5' end of widely expressed genes, including promoter, first exon, and first intron. In contrast, genomes of the MCF-7 and MDA-MB-231 cell lines show extensive hypomethylation in the intragenic and intergenic regions whereas the primary tumor exhibits a pattern between those of the normal tissue and the cell lines. A striking characteristic of tumor cell lines is the presence of megabase-sized hypomethylated zones. These hypomethylated zones are associated with large genes, fragile sites, evolutionary breakpoints, chromosomal rearrangement breakpoints, tumor suppressor genes, and with regions containing tissue-specific gene clusters or with gene-poor regions containing novel tissue-specific genes. Correlation with microarray analysis shows that genes with a hypomethylated sequence 2 kb up- or downstream of the transcription start site are highly expressed, whereas genes with extensive intragenic and 3' untranslated region (UTR) hypomethylation are silenced. The method described herein can be used for large-scale screening of changes in the methylation pattern in the genome of interest.
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Project description:There is considerable interest in identifying target genes and chromatin binding sites for transcription factors in a genome-wide manner. Such information may become useful in diagnosis and treatment of disease, drug target identification, and for prognostication. In cancer diagnosis, patterns of transcription factor binding to specific regulatory chromatin elements are expected to complement and enhance current diagnostic predictions of tumor behavior based on protein and mRNA analyses. Signal transducer and activator of transcription-5 (Stat5) is a cytokine-activated transcription factor implicated in growth and progression of many malignancies, including hematopoietic, prostate, and breast cancer. We have explored immunoaffinity purification of Stat5-bound chromatin from breast cancer cells to identify Stat5 target sites in an unbiased, genome-wide manner.In this report, we evaluate the efficacy of a Stat5-bound chromatin library to identify valid Stat5 chromatin binding sites within the oncogenome of T-47D human breast cancer cells. A general problem with cloning of immunocaptured, transcription factor-bound chromatin fragments is contamination with non-specific chromatin. However, using an optimized strategy, five out of ten randomly selected clones could be experimentally verified to bind Stat5 both in vitro and in vivo as tested by electrophoretic mobility shift assay and chromatin immunoprecipitation, respectively. While there was no binding to fragments lacking a Stat5 consensus binding sequence, presence of a Stat5 binding sequence did not assure binding.A chromatin library coupled with experimental validation may productively identify novel in vivo Stat5 chromatin binding sites in cancer, including abnormal regulatory sites in tumor-specific neochromatin.
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Project description:The EVI1 gene codes for a transcription factor with important roles in development and leukemogenesis. Overexpression of EVI1 in acute myeloid leukemia (AML) is one of the worst prognostic factors in patients with and without 3q26 rearrangements. Evi1 acts in several pathways through the interaction with proteins with important functions in hematopoiesis; however, the role of Evi1 as a transcription factor is not well known, and only some Evi1 target genes have been identified in mice. Our aim was to investigate the pathways and direct target genes of EVI1. Differential expression profiles after EVI1 knockdown allowed us to identify 125 genes involved in cell growth, differentiation and signal transduction that could be related to EVI1. Moreover, we looked for potential EVI1 binding sites within the region 1000 bp upstream of the transcription start sites of all human genes. We selected a total of 70 genes from the bioinformatics search, genes related to EVI1 by literature, and genes differentially expressed in the expression array. ChIP in the TF1 and HEL cell lines with two EVI1 antibodies demonstrated that EVI1 binds to the proximal promoter regions of 18 of these genes, most of them involved in important differentiation and proliferation pathways, confirming the important role of EVI1. Interestingly, EVI1 binds to the proximal region of its promoter, suggesting that it could be regulating its own transcription. Further functional studies are in progress. These data provide a starting point for further studies aimed at uncovering the mechanism for EVI1-induced transformation leukemias. Keywords: Gene expression analysis after transient knockdown of EVI1. 12 samples. Three replicates per experimental condition. Two cell lines (HTB-58, TF-1). Transient EVI1 knockdown using anti-EVI1 siRNA molecules vs. control siRNA.
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Project description:The upstream binding transcription factor (UBTF, also called UBF) is thought to function exclusively in RNA polymerase I (Pol I)-specific transcription of the ribosomal genes. We recently reported in Sanij et al. (2014) [1] that the two isoforms of UBF (UBF1/2) are enriched at Pol II-transcribed genes throughout the mouse and human genomes. By using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) of UBF1/2, Pol I, Pol II, H3K9me3, H3K4me4, H3K9ac and H4 hyperacetylation, we reported a correlation of UBF1/2 binding with enrichments in Pol II and markers of active chromatin. In addition, we examined a functional role for UBF1/2 in mediating Pol II transcription by performing expression array analysis in control and UBF1/2 depleted NIH3T3 cells. Our data demonstrate that UBF1/2 bind highly active Pol II-transcribed genes and mediate their expression without recruiting Pol I. Furthermore, we reported ChIP-sequencing analysis of UBF1/2 in immortalized human epithelial cells and their isogenically matched transformed counterparts. Here we report the experimental design and the description of the ChIP-sequencing and microarray expression datasets uploaded to NCBI Sequence Research Archive (SRA) and Gene Expression Omnibus (GEO).
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Project description:By performing chromatin immunoprecipitation coupled with ultra-high-throughput sequencing (ChIP-seq), we find that RAP1 binds to telomeres as well as to extra-telomeric sites through the (TTAGGG)2 consensus motif. Extra-telomeric RAP1 binding sites are particularly abundant at subtelomeric regions, and this is in agreement with preferential deregulation of subtelomeric genes in Rap1-deficient cells. Significantly, more than 70% of extratelomeric RAP1 binding sites are located in the vicinity of known genes and about 40% of the genes deregulated in Rap1-null cells contain binding sites for RAP1, suggesting a role of RAP1 in transcriptional control.
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