The physiological functions of vitamin D are mediated by its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) activating the transcription factor vitamin D receptor (VDR). In THP-1 human monocytes we demonstrated epigenome-wide effects of 1,25(OH)2D3 at 8979 loci with significantly modulated chromatin accessibility. Maximal chromatin opening was observed after 24 h, while after 48 h most sites closed again. The chromatin-organizing protein CTCF bound to 14% of the 1,25(OH)2D3-sensitive chromatin regions. Interestingly, 1,25(OH)2D3 affected the chromatin association of CTCF providing an additional mechanism for the epigenome-wide effects of the VDR ligand. The 1,25(OH)2D3-modulated transcriptome of THP-1 cells comprised 1284 genes, 77.5% of which responded only 24 h after stimulation. During the 1,25(OH)2D3 stimulation time course the proportion of down-regulated genes increased from 0% to 44.9% and the top-ranking physiological function of the respective genes shifted from anti-microbial response to connective tissue disorders. The integration of epigenomic and transcriptomic data identified 165 physiologically important 1,25(OH)2D3 target genes, including HTT and NOD2, whose expression can be predicted primarily from epigenomic data of their genomic loci. Taken together, a large number of 1,25(OH)2D3-triggered epigenome-wide events precede and accompany the transcriptional activation of target genes of the nuclear hormone.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872072 | PMC |
| http://dx.doi.org/10.1093/nar/gkv1519 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Exeter, Exeter, Devon, United Kingdom.
Background: Huntington's disease (HD) is an autosomal dominant condition causing severe neurodegeneration in the striatum and the entorhinal cortex (EC). An epigenome wide association study of DNA methylation in HD by our group, identified potential hypomethylation at the PTGDS gene in the striatum. We aimed to validate this result through pyrosequencing, examining the locus in fine detail, and to assess the signal specificity by profiling multiple neurodegenerative diseases.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is neuropathologically characterized by amyloid-β (Aβ) plaques and tau neurofibrillary tangles often quantified by Thal phase and Braak stage, respectively. Aβ also frequently deposits in the cerebrovasculature with severity categorized by a cerebral amyloid angiopathy (CAA) score. These and related measures often show high variability within AD suggesting distinct underlying mechanisms.
View Article and Find Full Text PDFLinking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study.
BMC Genomics
December 2024
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbial pathways using data generated by shotgun metagenomic sequencing (n = 683).
View Article and Find Full Text PDFEpigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.
Genome Med
December 2024
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Article Synopsis
- The study explores the biological differences linked to PTSD by examining DNA methylation changes in blood, suggesting they could indicate susceptibility or effects of trauma.
- Conducted by the Psychiatric Genomics Consortium, the research included nearly 5,100 participants to identify specific genetic markers associated with PTSD.
- Results showed 11 significant CpG sites related to PTSD, with some also showing correlations between blood and brain tissue methylation, highlighting their potential role in understanding PTSD biology.
Epigenome-wide mediation analysis of the relationship between psychosocial stress and cardiometabolic risk factors in the Health and Retirement Study (HRS).
Clin Epigenetics
December 2024
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Background: Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!