In vivo contribution of Cyp24a1 promoter vitamin D response elements
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1150259 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30316834_1.fastq.gz | Fastqsanger.gz | |||
| SRR30316834_2.fastq.gz | Fastqsanger.gz | |||
| SRR30316835_1.fastq.gz | Fastqsanger.gz | |||
| SRR30316835_2.fastq.gz | Fastqsanger.gz | |||
| SRR30316836_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 62 |
Similar Datasets
Project description:CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3 and fibroblast growth factor 23 (FGF23) and potently suppressed by PTH to control the circulating levels of 1,25(OH)2D3. Cyp24a1 is controlled by a pair of promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) enhancers. The downstream 1 region of Cyp24a1 (DS1) enhancer is kidney-specific and responsible for PTH and FGF23 actions, and the downstream 2 region of Cyp24a1 enhancer responds to 1,25(OH)2D3 in all tissues. Despite this knowledge, in vivo contributions of the PRO VDREs to basal expression, FGF23 activation, and PTH suppression of Cyp24a1 remain unknown. In this study, we selectively mutated the PRO VDREs in the mouse to address these questions. We found mutation of the VDREs leads to a dramatic loss of VDR occupancy, a reduction of 1,25(OH)D3-induced kidney Cyp24a1 expression, and near elimination of intestinal Cyp24a1 induction. FGF23 induction of Cyp24a1 was reduced but not eliminated and still showed a synergistic increase with 1,25(OH)2D3. PTH suppression of Cyp24a1 was unchanged, despite minor reductions in total for phosphorylated cAMP-response element binding protein occupancy. Finally, VDR recruitment was dramatically reduced across the DS enhancers in the Cyp24a1 locus. Taken together, our data suggest a cooperative relationship between the DS and PRO enhancers in the regulation of Cyp24a1 by 1,25(OH)2D3 and FGF23 and points to the DS1 region as a crucial basal switch for Cyp24a1 activity that further defines the interconnected genomic control in vitamin D catabolism.
2024-08-25 | GSE275331 | GEO
Project description:Enhancer Cis Elements Instruct Promoter-Enhancer Interaction, Promoter-Enhancer Insulation and Compartmental Segregation
| PRJNA881254 | ENA
Project description:Introduction: Biologically active vitamin D (1,25-dihydroxyvitamin D or 1,25D) has emerged as a key regulator of human innate immunity. 1,25D signaling in macrophages strongly induces the expression of neutrophil chemoattractants, such as IL-8/CXCL8. Meta-analysis of vitamin D-regulated expression profiles has suggested that 1,25D may regulate granule formation in granulocytic cells. Here, we have examined the effects of 1,25D signaling on human neutrophil gene expression, alone and in combination with the inflammatory signal lipopolysaccharide (LPS). These studies are of interest because, whereas 1,25D signaling boosts innate immunity, it is anti-inflammatory. Methods and results: We determined the effects of 1,25D alone and in combination with LPS on gene expression of primary human neutrophils by RNAseq. LPS did not affect or slightly enhanced the expression of several well-characterized 1,25D-target genes, but strongly suppressed that encoding the 1,25D catabolic enzyme CYP24A1. Chromatin immunoprecipitation (ChIP) assays revealed that 1,25D- dependent vitamin D receptor (VDR) binding to the major CYP24A1 enhancer was eliminated in neutrophils treated with LPS, whereas binding to other 1,25D-target genes was unaffected. Notably, LPS induced binding of transcriptional repressors MAFF and BACH1 to the major CYP24A1 enhancer region. In other studies, pathway analyses revealed that 1,25D suppressed LPS-induced genes encoding inflammatory proteins. In addition, RNAseq and confirmatory RT/qPCR studies revealed that 1,25D, both on its own and in combination with LPS, increased mRNA expression of genes encoding antimicrobial components of secretory granules, including that encoding cathelicidin antimicrobial peptide (CAMP). Consistently, exposure of neutrophils to 1,25D enhanced bacterial killing, as revealed by a 20-25% reduction in E. coli colonies incubated with 1,25D-treated neutrophil conditioned media. The increased bacterial killing by 1,25D is mediated by 1,25D- induced secretion of cathelicidin, as an antibody against LL-37, the active form of cathelicidin, blocked antimicrobial activity. Discussion: Collectively, the data suggest that LPS prolongs vitamin D signaling by suppressing expression of the 1,25D catabolic enzyme CYP24A1. 1,25D signaling in the presence of LPS attenuates the expression of several genes associated with LPS inflammatory responses, whereas 1,25D in the absence or presence of LPS enhances the release of antibacterial proteins secreted by neutrophils in response to infection.
2025-09-22 | GSE308684 | GEO
Project description:Differential contribution of p300 and CBP to regulatory elements in mESCs
| PRJNA577734 | ENA
Project description:Enhancers harbor instructions encoded for the interactions between cis-elements and transcription factors to orchestrate lineage specific gene programs. Here we developed a modified method for chromosome conformation capture (3C), named MID Hi-C, to reveal how in mouse embryonic stem cells differential cooperation of enhancers and the chromatin remodeler BAF, as instructed by the underlying transcription factor motifs, modulate enhancer-promoter communication. We show that BAF-dependent enhancers permit genomic interactions beyond enhancer boundaries. BAF-dependent enhancers do not dictate genomic interactions within enhancer-promoter loop domains but rather act to instruct remote enhancer-promoter communication. In contrast, BAF-independent enhancers interact with promoter regions within tightly insulated enhancer-promoter loop domains that are marked by promoter and enhancer boundary elements. In addition, enhancer activeness modulated by BAF enforces compartment segregation. Based on these observations, we propose that enhancer cis elements instruct with great precision BAF-induced enhancer-promoter communication and compartmental segregation.
2023-12-31 | GSE213501 | GEO
Project description:Antimicrobial proteins form an essential chemical barrier that protects the intestinal epithelium from microbial invasion. REG3 family antimicrobial lectins are prominently induced by the microbiota, but how nutritional cues intersect with microbial signals to regulate their expression is poorly understood. Vitamin A plays a central role in mucosal adaptive immunity, but its contribution to epithelial innate immunity is unclear. Here, we show that dietary vitamin A promotes expression of REG3 antimicrobial lectins, including REG3G, in intestinal epithelial cells from both mice and humans. Vitamin A–dependent induction of REG3G expression is driven by retinoic acid and requires signaling through retinoic acid receptors (RARs). Mechanistically, RARs directly bind the Reg3g promoter adjacent to a binding site for STAT3, the transcription factor that transduces microbial signals, thereby integrating nutritional and microbial inputs at the level of REG3G transcription. Extending these findings, we demonstrate that vitamin A–retinoic acid signaling similarly promotes expression of α-defensin antimicrobial proteins. Together, these results define a transcriptional mechanism by which vitamin A enhances epithelial antimicrobial defenses to strengthen mucosal innate immunity.
2026-03-08 | GSE318054 | GEO
Project description:Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms. CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis-regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. We found the boundaries of the CFTR TAD are conserved among diverse cell types and are dependent on CTCF and cohesin complex. Removal of an upstream CTCF-binding insulator alters the interaction profile, but has little effect on CFTR expression. Within the TAD, intronic enhancers recruit cell-type selective transcription factors and deletion of a pivotal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structure. Examination of open chromatin region in Caco2 (colorectal adenocarcinoma cells), HBE (primary human bronchial epithelial cells), and primary adult human epididymis cells
2016-01-07 | E-GEOD-74709 | biostudies-arrayexpress
Project description:Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes
| PRJNA922468 | ENA
Project description:Differential contribution of p300 and CBP to regulatory elements in mESCs [ChIP-seq]
| PRJNA577735 | ENA
Project description:Differential contribution of p300 and CBP to regulatory elements in mESCs [ATAC-seq]
| PRJNA577736 | ENA