Genomic and epigenomic 1α,25(OH)2D3 responses in human colonic organoids
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PROVIDER: PRJNA683597 | ENA |
REPOSITORIES: ENA
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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:Growth plate chondrocytes are regulated by numerous factors and hormones as they mature during endochondral bone formation. Chondrocytes in the growth plate’s growth zone (GC cells) produce and export matrix vesicles (MVs) under the regulation of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. 1α,25(OH)2D3 secreted by the cells acts on the MV membrane, releasing its contents. This study examined the regulatory role 1α,25(OH)2D3 has over the production and packaging of microRNA into MVs by GC cells and the ability to release microRNA from MVs once produced. We treated GC cells with 1α,25(OH)2D3 and then sequenced the microRNA in the cells and MVs. We also treated MVs with 1α,25(OH)2D3 and determined if the microRNA was released. To assess whether MVs can act directly with chondrocytes and if this is regulated by 1α,25(OH)2D3, we stained MVs with a membrane dye and treated GC cells with them. 1α,25(OH)2D3 regulated the production and packaging of microRNA into matrix vesicles. MVs did not release microRNA when treated with 1α,25(OH)2D3, indicating a heterogeneous MV population or a protective factor. Stained MVs were endocytosed by GC cells and this was increased with 1α,25(OH)2D3 treatment. This study adds new regulatory roles for 1α,25(OH)2D3 with respect to packaging and transport of MV microRNAs.
2021-12-06 | GSE190020 | GEO
Project description:The nuclear hormone 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) regulates its target genes via activation of the transcription factor vitamin D receptor (VDR) far more specifically than the chromatin modifier trichostatin A (TsA) via its inhibitory action on histone deacetylases. We selected the thrombomodulin gene locus with its complex pattern of three 1α,25(OH)2D3 target genes, five VDR binding sites and multiple histone acetylation and open chromatin regions as an example to investigate together with a number of reference genes, the primary transcriptional responses to 1α,25(OH)2D3 and TsA. Transcriptome-wide, 18.4% of all expressed genes are either up- or down-regulated already after a 90 min TsA treatment; their response pattern to 1α,25(OH)2D3 and TsA sorts them into at least six classes. TsA stimulates a far higher number of genes than 1α,25(OH)2D3 and dominates the outcome of combined treatments. However, 200 TsA target genes can be modulated by 1α,25(OH)2D3 and more than 1000 genes respond only when treated with both compounds. The genomic view on the genes suggests that the degree of acetylation at transcription start sites and VDR binding regions may determine the effect of TsA on mRNA expression and its interference with 1α,25(OH)2D3. Our findings may have implications on dual therapies using chromatin modifiers and nuclear receptor ligands.
2012-10-25 | GSE36323 | GEO
Project description:Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3 Keywords = macrophages Keywords = VDR Keywords = activated vitamin D3 Keywords = IFNgamma Keywords = KO mice Keywords: dose response
2005-04-21 | GSE2421 | GEO
Project description:In this study, we compared the modulation of the transcriptome of human PBMCs by the vitamin D metabolites 25-hydroxyvitamin D3 (25(OH)D3), 25(OH)D2 and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3).
2022-06-21 | GSE199273 | GEO
Project description:B10.PL mice with severe (stage 2.5-3) experimental autoimmune encephalomyelitis were treated with placebo or 200 ng 1,25(OH)2D3. Six hours later, the spinal cords were harvested and mRNA was extracted for microarray analysis. Naive mice serve as controls. Individual samples were hybridized to individual microarrays. Keywords = Experimental autoimmune encephalomyelitis Keywords = multiple sclerosis Keywords = 1 Keywords = 25(OH)2D3 Keywords: repeat sample
2003-12-01 | GSE842 | GEO
Project description:We carried out a genome-wide investigation of the primary transcriptional targets of 1α,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1α,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1α,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1α,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1α,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1α,25(OH)2D3 treatment provides a resource of primary 1α,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells. ChIP-Seq for trimethylated histone H3K4 with SKBr3 cells treated for 2h with 100nM 1α,25(OH)2D3 or vehicle as control.
2014-06-25 | E-GEOD-54856 | biostudies-arrayexpress
Project description:We carried out a genome-wide investigation of the primary transcriptional targets of 1α,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1α,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1α,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1α,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1α,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1α,25(OH)2D3 treatment provides a resource of primary 1α,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells.
2014-06-25 | GSE54856 | GEO
Project description:Neonatal keratinocytes from African American donors of passage 2 or 3 were treated with 20,23(OH)2D3, 1,25(OH)2D3 or 0.1% ethanol (control) for 6 and 24 hours. The cells were harvested separately, RNA isolated and submitted for microarray analysis at the Molecular Resources Center at the UTHSC.
2018-07-19 | GSE117351 | GEO
Project description:1,25(OH)2D3 upregulated lncRNA
| PRJNA741924 | ENA