Similar Datasets
Project description:VDR ChIP-Seq on colonic human organoids
| PRJNA419552 | ENA
Project description:Treatment with calcitriol, a specific VDR agonist, augmented the heterodimerization between VDR and RXR. We also wanted to investigate its impact on VDR binding to genomic regions. ChIP-seq experiments were carried out with the human monocytic THP-1 cell line under either vehicle (1:1 DMSO-ethanol) or calcitriol (100 nM) treatment conditions. Our finding is that calcitriol may have both a stimulatory or an inhibitory effect on VDR binding depending on the presence of its specific response element (VDRE), a less specific nuclear receptor (NR) half-site or absence thereof ("None"). Upon calcitriol activation, VDRE-containing genomic regions showed considerably higher occupancies on average than in the control, vehicle-treated sample. A similar induction, but to a much lesser extent, was detected for the NR half-site-containing regions. In contrast, genomic regions not containing any of these specific response elements did not show any induction upon calcitriol treatment; they rather showed a decrease of binding in promoter regions. We can conclude that ligand-induced heterodimerization and binding of the NR to its response elements are correlated events.
2020-05-16 | GSE150652 | GEO
Project description:Analysis of acute effects of ligand-treatment on vitamin D receptor binding genome-wide using ChIP-seq. THP-1 monocytic leucemia cells were treated with 1?,25(OH)2D3 (1,25D) or left unstimulated to investigate the acute effects of VDR chromatin occupancy. We identified in total 2340 VDR binding sites with and without the ligand. Without the ligand, there is a considerable presence of VDR already on the chromatin. However, upon a short (40 min) ligand treatment VDR shifts from sites that rarely contain a DR3 type element to sites that frequently contain one or more DR3-type element. Genome-wide identification of VDR binding in THP-1 cells at the unstimulated state and after 40 min ligand (10 nM 1?,25(OH)2D3 (1,25D, calcitriol)) treatment.
2011-08-17 | E-GEOD-27437 | biostudies-arrayexpress
Project description:1,25(OH)D3 effect on colonic organoids from wt and VDR KO mice
| PRJNA414728 | ENA
Project description:The genome-wide analysis of the binding sites of the transcription factor vitamin D receptor (VDR) is essential for a global appreciation the physiological impact of the nuclear hormone 1M-NM-1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide analysis of lipopolysaccharide (LPS)-polarized THP-1 human monocytic leukemia cells via chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq) resulted in 1,318 high-confidence VDR binding sites, of which 789 and 364 occurred uniquely with and without 1,25(OH)2D3 stimulation, while only 165 were common. We re-analyzed five public VDR ChIP-seq datasets with identical peak calling settings (MACS, version 2) and found in total 23,409 non-overlapping VDR binding sites, 75% of which are unique within the six analyzed cellular models. LPS-differentiated THP-1 cells have 22% more genomic VDR locations than undifferentiated cells and both cell types display more overlap in their VDR locations than the other investigated cell types. In general, the intersection of VDR binding profiles of ligand-stimulated cells is higher than those of unstimulated cells. De novo binding site searches and DR3-type binding site screening using HOMER of the six VDR ChIP-seq datasets suggest that DR3 sites are strongly associated with the ligand-responsiveness of VDR occupation. Importantly, all VDR ChIP-seq datasets display the same relationship between the VDR occupancy and the percentage of DR3-type sequences below the peak summits. The comparative analysis of six VDR ChIP-seq datasets demonstrated that the mechanistic basis for the action of the VDR is independent of the cell type. Only the minority of genome-wide VDR binding sites contains a DR3-type sequence. Moreover, the total number of identified VDR binding sites in each ligand-stimulated cell line inversely correlates with the percentage of peak summits with DR3 sites. Systematic reanalysis of 5 published VDR ChIP-seq datasets together with a new dataset from 24 h LPS-treated THP-1 cells at the unstimulated state and after 80 min ligand (10 nM 1M-NM-1,25(OH)2D3 (1,25D, calcitriol)) treatment. See GSM1280896 and GSM1280896 Sample records for data processing information. GSE53041_README.txt has additional details.
2014-11-14 | E-GEOD-53041 | biostudies-arrayexpress
Project description:We reported transcriptional characterization of Treg cells, Tconv cells, and DCs isolated from coloinc lamina propria of Vdr WT- or Vdr KO-Foxp3 reporter mice. We also reported transcriptional characterization of colonic ECs isolated from Vdr WT- or Vdr KO-Foxp3 reporter mice.
2019-12-31 | GSE137405 | GEO
Project description:VitaminD deficiency has been related to a higher incidence of colorectal cancer. In order to further study the effect of VDR and its ligand as genome modulators we established stem cell enriched cultures of wt and VDR KO mice, treated with the active metabolite of Vitamin D and analyzed the changes in total RNA expression.
2019-07-21 | GSE105117 | GEO
Project description:Background & Aims: Active vitamin D, 1α,25(OH)2D3, is a nuclear hormone with roles in colonic homeostasis and carcinogenesis, yet mechanisms underlying these effects are incompletely understood. Human organoids are an ideal system to study genomic and epigenomic host-environment interactions. Here, we utilize human colonic organoids to measure 1α,25(OH)2D3 responses on genome-wide gene expression and chromatin accessibilityover time. Methods: Human colonic organoids were cultured and treated in triplicate with either 100nM 1α,25(OH)2D3 or vehicle control for 4 and 18 hours (h) for chromatin accessibility, and 6 and 24hfor gene expression. DNA and RNA were extracted for ATAC- and RNA-sequencing, respectively. Differentially accessible peaks were analyzed using DiffBind and EdgeR; differentially expressed genes were analyzed using DESeq2. Motif enrichment was determined using HOMER. Results: At 6h and 24h, 2870 and 2721 differentially expressed genes, respectively (FDR<5%) were identified with overall stronger responses with 1α,25(OH)2D3. Similarly, 1α,25(OH)2D3 treatment led to stronger chromatin accessibility especially at 4h. The vitamin D receptor (VDR) motif was strongly enriched among open chromatin peaks with 1α,25(OH)2D3 treatment accounting for 30.5% and 11% of target sequences at 4h and 18h, respectively (FDR<1%). A number of genes such as CYP24A1, FGF19, MYC, FOS and TGFBR2 showed significant transcriptional and chromatin accessibility responses to 1α,25(OH)2D3 treatment with open chromatin located distant from promoters for some gene regions. Conclusions: Assessment of chromatin accessibility and transcriptional responses to 1α,25(OH)2D3 yielded new observations about vitamin D genome-wide effects in the colon facilitated by application of human colonic organoids. This framework can be applied to study host-environment interactions between individuals and populations in future.
2020-12-09 | GSE162856 | GEO
Project description:Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide a unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using organoids from human healthy tissue. Culture of normal patient-derived colon organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the g-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 and DBZ showing only weak signals of cell differentiation. We also investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on differentiation. Calcitriol attenuated the effects of the BMP4 and DBZ on normal colon organoids, with reduced expression of differentiation genes and phenotype. Consistently, in normal organoids, calcitriol inhibited early signaling by BMP4 as assessed by reduction of the level of phospho-SMAD1/5/8. Our results show that BMP and Notch signaling play key roles in human colon stem cell differentiation to the enterocytic and goblet cell lineages and that calcitriol modulates these processes favoring stemness features.
2024-04-15 | GSE248274 | GEO
Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates
2015-08-01 | E-GEOD-64656 | biostudies-arrayexpress