Quantitative profiling of drug-responsive regulatory activity at the human genome scale
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114063 | GEO | 2018/11/06
REPOSITORIES: GEO
Similar Datasets
Project description:Changes in epigenetic marks, such as DNA methylation, in cancer subclones may increase their fitness, leading to cancer progression, treatment resistance, and worse prognosis. We have developed DXM, a novel computational method to identify subpopulation methylation events from bisulfite sequencing data of a heterogeneous sample DXM does not require prior knowledge of the number of cell types or what cell types to expect in the sample, and it outperforms existing methods. To further validate our method, we conducted genomic bisulfite sequencing on four primary DLBCL samples, obtaining data from >4.9 million CpGs at 50x average coverage. DXM predictions of subpopulation methylation profiles in these samples were confirmed in FACS-sorted CD4+ and CD19+ cells. Thus, we have developed a method, DXM, that can identify subpopulation methylation profiles in heterogeneous samples
2021-06-04 | GSE130556 | GEO
Project description:The transition to flowering in plants is controlled by a regulatory network that responds to both developmental and environmental signals. The MADS-box genes FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE (SVP) are major flowering repressors that enhance responses to environmental cues such as winter temperatures, high ambient temperatures and photoperiod. FLC and SVP physically interact in vivo and mutation of each gene causes early flowering while the double mutant is more extreme. The molecular mechanisms underlying these genetic interactions are mostly unknown. We addressed the regulatory input of these two key transcription factors (TFs) both individually and as a complex at the genome-wide level through ChIP-seq and microarray expression analysis in single and double mutants. Analysis of each TF demonstrated that the complex acts predominantly via functional redundancy in the repression of flowering. SVP and FLC bind to the same regions of the flowering genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and FLOWERING LOCUS T (FT) but do not require the presence of the other to bind. However, genome-wide identification of SVP and FLC occupancy events revealed that their binding scenarios are quantitatively and qualitatively affected by the presence of the cognate partner. A subgroup of genes whose regulation by these TFs depends exclusively on combinatorial binding of both proteins was identified, demonstrating a qualitatively essential role of the SVP-FLC complex. Some of these genes are involved in the control of flowering through direct and indirect regulation of Gibberellin-related processes. Cis-regulatory elements enriched only at such complex-bound sites were identified. Thus the regulatory output mediated by SVP and FLC reveals substantial flexibility, leading to dependent and independent DNA binding that enables additive, cooperative and repressive modes of co-regulation. In total 48 samples; 24 leaf samples corresponding to two different growing conditions, 24 apex samples corresponding to two different growing conditions.
2015-01-11 | E-GEOD-57416 | biostudies-arrayexpress
Project description:The yeast S. cerevisiae does not require selenium for growth, so it is an excellent model to investigate the toxicity of this element without interference from its requirement as growth factor as occurs in animal cells. Exposure to selenite interferes with the yeast iron metabolism. Aft2 is a transcription factor related (with Aft1) to maintenance of iron homeostasis. We have found that aft2 cells are highly sensitive to selenite (a common environmental source for selenium). In these experiments we investigate the transcriptional response to a sub-lethal dose of selenite in wild type and aft2 cells. Our results show that the aft2 mutation strongly potentiates the transcriptional response to selenite, showing induction of many genes related to the responses to oxidative stress and DNA damage.
2015-12-31 | GSE70835 | GEO
Project description:Enhancers and silencers often depend on the same transcription factors (TFs) and are imperfectly distinguished from each other by genomic assays of TF binding or chromatin state. To identify sequence features that define enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX and found instances of enhancer, silencer, or no activity. Both enhancers and silencers contain more TF motifs than inactive sequences, but enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. Our results indicate that enhancers contain motifs for a diverse but degenerate collection of TFs, while silencers depend on a smaller and less diverse collection of TFs.
2021-01-30 | GSE165812 | GEO
Project description:During fasting transcriptional programs lead to glucose and ketone production. The major TFs, their crosstalk and the enhancers driving it are unknown. We show that fasting massively reorganizes liver chromatin to expose 'fasting enhancers'. By tracking TF footprints, we implicated the major TFs regulating fuel production by two modules. The ketogenic module is executed by a temporally-organized TF cascade. Conversely, in the gluconeogenic module glucocorticoid receptor (GR) augments cAMP-response element-binding protein (CREB) activity in an enhancer-selective manner. Using genomics and single-molecule tracking, we show that GR enhances the number of bound CREB molecules and the quantity, intensity and accessibility of CREB binding sites; leading to synergistic gene expression and glucose production. Our findings reveal that TFs dynamically and cooperatively respond to environmental signals to restore homeostasis.
2016-12-20 | GSE72084 | GEO
Project description:DNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses. In this study, we examined single-base resolution methylomes of Populus under control and drought stress conditions using high-throughput bisulfite sequencing for the first time. Our data showed methylation levels of methylated cytosines, upstream2kp, downstream2kb, and repeatitive sequences significantly increased after drought treatment in Populus. Interestingly, methylation in 100 bp upstream of the transcriptional start site (TSS) repressed gene expression, while methylations in 100 – 2000bp upstream of TSS and within the gene body were positively associated with gene expression. Integrated with the transcriptomic data, we found that all cis-splicing genes were non-methylated, suggesting that DNA methylation may not associate with cis-splicing. However, our results showed that 80% of trans-splicing genes were methylated. Moreover, we found 1156 transcription factors (TFs) with reduced methylation and expression levels and 690 TFs with increased methylation and expression levels after drought treatment. These TFs may play important roles in Populus drought stress responses through the changes of DNA methylation. Taken together, these findings may provide valuable new insight into our understanding of the interaction between gene expression and methylation of drought responses in Populus. Methylomes of Poplar response to drought
2014-08-18 | E-GEOD-55087 | biostudies-arrayexpress
Project description:Sulphur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulphur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulphate starvation have been studied in the past, knowledge of the regulation of sulphur metabolism is still fragmentary. This work focuses on the discovery of candidates for regulatory genes such as transcription factors (TFs) using ‘omics technologies. For this purpose a short term sulphate-starvation / re-supply approach was used. ATH1 microarray studies and metabolite determinations yielded 21 TFs which responded more than 2-fold at the transcriptional level to sulphate starvation. Categorization by response behaviors under sulphate-starvation / re-supply and other nutrient starvations such as nitrate and phosphate allowed determination of whether the TF genes are specific for or common between distinct mineral nutrient depletions. Extending this co-behavior analysis to the whole transcriptome data set enabled prediction of putative downstream genes. Additionally, combinations of transcriptome and metabolome data allowed identification of relationships between TFs and downstream responses, namely, expression changes in biosynthetic genes and subsequent metabolic responses. Effect chains on glucosinolate and polyamine biosynthesis are discussed in detail. The knowledge gained from this study provides a blueprint for an integrated analysis of transcriptomics and metabolomics and application for the identification of uncharacterized genes.
2015-01-15 | GSE64972 | GEO
Project description:Sulphur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulphur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulphate starvation have been studied in the past, knowledge of the regulation of sulphur metabolism is still fragmentary. This work focuses on the discovery of candidates for regulatory genes such as transcription factors (TFs) using M-bM-^@M-^Xomics technologies. For this purpose a short term sulphate-starvation / re-supply approach was used. ATH1 microarray studies and metabolite determinations yielded 21 TFs which responded more than 2-fold at the transcriptional level to sulphate starvation. Categorization by response behaviors under sulphate-starvation / re-supply and other nutrient starvations such as nitrate and phosphate allowed determination of whether the TF genes are specific for or common between distinct mineral nutrient depletions. Extending this co-behavior analysis to the whole transcriptome data set enabled prediction of putative downstream genes. Additionally, combinations of transcriptome and metabolome data allowed identification of relationships between TFs and downstream responses, namely, expression changes in biosynthetic genes and subsequent metabolic responses. Effect chains on glucosinolate and polyamine biosynthesis are discussed in detail. The knowledge gained from this study provides a blueprint for an integrated analysis of transcriptomics and metabolomics and application for the identification of uncharacterized genes. Arabidopsis seedlings were grown in 30 mL of sterile liquid full nutrition (FN) medium (3 mM sulphate) or 150 M-NM-<M sulphate medium. Transferring pre-grown 7-days old seedlings to a sulphate depleted medium (0 M-NM-<M sulphate) assured immediate and continued sulphate starvation during the next two days of plant cultivation. On day 9 subsets of the sulphate depleted cultures were supplied with sulphate (500 M-NM-<M) and samples taken 30 min and 3 hours after re-supply. Four time points (full nutrition (FN), plants starved for 48 h (-S), plants re-supplied with sulphate for 30 minutes (30M-bM-^@M-^Y S) and plants re-supplied with sulphate for 3 hours (3 h S)) were subjected to the microarray analysis. Two biological repetitions of each sample were analyzed.
2015-01-15 | E-GEOD-64972 | biostudies-arrayexpress
Project description:Many of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, we examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures. Duplication of TFs can confer an extension of transcriptional regulatory structures for target genes by providing new regulatory relationships between duplicated TFs and new or old target genes. To examine the nature of the extension in the regulatory structure, we performed gene expression profiling of Arabidopsis root tissues obtained from wild-type (WT) and deletion mutants of three type-B ARR1, 10, and 12. To examine how the extended regulatory structures by the duplicated ARR TFs are utilized for the responses to external CK, we generated gene expression profiles of WT Arabidopsis roots treated with mock or exogenous CK for 1 hour. Total RNAs were isolated from two biological replicates at each condition and used to measure gene expression level.
2015-02-03 | E-GEOD-62597 | biostudies-arrayexpress
Project description:Mapping transcriptional regulatory networks is difficult because many transcription factors (TFs) are activated only under specific conditions. We describe a generic strategy for identifying genes and pathways induced by individual TFs that does not require knowledge of their normal activation cues. Microarray analysis of 55 yeast TFs that caused a growth phenotype when overexpressed showed that the majority caused increased transcript levels of genes in specific physiological categories, suggesting a mechanism for growth inhibition. Induced genes typically included established targets and genes with consensus promoter motifs, if known, indicating that these data are useful for identifying potential new target genes and binding sites. We identified the sequence 5'-TCACGCAA as a binding sequence for Hms1p, a TF that positively regulates pseudohyphal growth and previously had no known motif. The general strategy outlined here presents a straightforward approach to discovery of TF activities and mapping targets that could be adapted to any organism with transgenic technology. Keywords: phenotypic activation
2006-09-14 | GSE5499 | GEO