Publications

Priman Alfred Fau, Antonio Neme, Sabine Seuter and Carsten Carlberg

Temporal stratification of promoter-proximalversus enhancer VDR binding directs vitaminD-responsive transcription

Epigenetics & Chromatin Volume 19, article number 26 (2026)

Background: The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activates the vitamin D receptor (VDR) in immune cells, altering the epigenome to drive diverse responses. However, how the temporal dynamics, genomic positioning, and inducibility of VDR binding are integrated to determine transcriptional outcomes remains incompletely understood.

Results: Here, we present a time-resolved analysis of VDR-mediated gene regulation in human THP-1 monocytes, integrating VDR ChIP-seq profiles at 40 min, 4, 8, and 24 h with matched transcriptome data following stimulation with 1,25(OH)2D3. Time-resolved VDR ChIP-seq revealed > 22,000 binding sites, with > 5,100 showing ligand-inducible occupancy that expanded over time. This expansion parallels a marked increase in vitamin D-responsive genes, evolving from a limited early response to a broad late transcriptional program. Using distance- and topologically associated domain-informed assignment strategies, we classify vitamin D target genes according to their spatial and temporal association with VDR binding, distinguishing promoter-proximal and enhancer-dominated regulatory architectures. Early vitamin D target genes are characterized by frequent VDR occupancy at transcription start site
regions, often supported by coordinated enhancer binding, whereas late-responsive genes are predominantly associated with distal enhancers or lack assignable VDR-driven regulatory models. Importantly, promoter‑proximal VDR binding is consistently stronger and more inducible than enhancer‑only binding and is associated with higher basal expression and greater transcriptional responsiveness.

Conclusions: Together, these findings define a hierarchical, multi-layered model of vitamin D signaling in which early, promoter-proximal VDR binding is strongly associated with establishment of a transcriptionally competent core program, while later enhancer-mediated and indirect mechanisms progressively expand and diversify the response.

Temporal stratification of promoter-proximalversus enhancer VDR binding directs vitaminD-responsive transcription [PDF]

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Eunike Velleuer, Carsten Carlberg

Fanconi anaemia as a human model of accelerated epigenetic and immune ageing

Ageing Research Reviews 2026, Volume 115

Fanconi anaemia (FA) is a DNA-repair disorder that compresses multiple hallmarks of ageing into childhood and early adulthood. Persistent genomic instability in FA precipitates oxidative stress, inflammatory remodelling, and metabolic reprogramming, which together erode epigenetic integrity and immune competence. Here we provide evidence FA-specific DNA-repair failure is linked to mitochondrial metabolism, nutrient-sensing networks, and immune dysfunction. In this context, we discuss how these interactions accelerate epigenetic drift and cancer susceptibility. We propose FA as a human “time-lapse” model to separate the sequence and interdependence of selected ageing hallmarks, such as genome instability, epigenetic deregulation, stem cell exhaustion, and immunosenescence, which together contribute to a markedly increased risk of early cancer development. We further highlight nutrigenomic mechanisms, including vitamin D-dependent chromatin remodelling and redox-sensitive cofactors, that modulate epigenetic states and immune resilience. Framing FA within the broader framework of ageing biology suggests testable biomarkers and precision-prevention strategies aimed at stabilising the epigenome, delaying carcinogenesis, and prolonging healthspan.

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Maciej Rybiński, Ranjini Ghosh Dastidar, Natalia Zawrotna, Emilia Gospodarska & Carsten Carlberg

Chromatin and transcriptional dynamics underlying the immune-modulatory effects of vitamin D3 in vivo

Scientific Reports volume 16, Article number: 2997 (2026)

Vitamin D₃ is an essential micronutrient that supports innate immunity and modulates adaptive responses, with in vitro studies implicating epigenetic mechanisms. Yet, in vivo evidence for such regulation remains scarce. Here, we assessed genome-wide epigenomic and transcriptomic responses to vitamin D₃ in a high responder from the VitDHiD repeated-measures, non-randomized interventional N-of-1 study, in which the participant received monthly oral boluses of 80,000 IU vitamin D₃ over three months. 

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Marianna Raczyk and Carsten Carlberg

From Sunlight to Signaling: Evolutionary Integration of Vitamin D and Sterol Metabolism

Metabolites 2026, 16(1), 74;

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics.

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