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Cited by 293Vitamin D Research StudiesGenomics and Chromatin DynamicsNuclear Receptors and Signaling

Vitamin D Receptor Signaling Mechanisms: Integrated Actions of a Well-Defined Transcription Factor

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Carlberg, Carsten, Campbell, Moray J.·2013·Steroids
DOI 10.1016/j.steroids.2012.10.019PMC PMC4668715
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Abstract

The main physiological actions of the biologically most active metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)), are calcium and phosphorus uptake and transport and thereby controlling bone formation. Other emergent areas of 1α,25(OH)(2)D(3) action are in the control of immune functions, cellular growth and differentiation. All genomic actions of 1α,25(OH)(2)D(3) are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980's. Thus, vitamin D signaling primarily implies the molecular actions of the VDR. In this review, we present different perspectives on the VDR that incorporate its role as transcription factor and member of the nuclear receptor superfamily, its dynamic changes in genome-wide locations and DNA binding modes, its interaction with chromatin components and its primary protein-coding and non-protein coding target genes and finally how these aspects are united in regulatory networks. By comparing the actions of the VDR, a relatively well-understood and characterized protein, with those of other transcription factors, we aim to build a realistic positioning of vitamin D signaling in the context of other intracellular signaling systems.

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  • Vitamin D, through its interaction with the vitamin D receptor (VDR), can modulate the activity of chromatin-modifying enzymes, including DNA methyltransferases (DNMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs), and can influence DNA methylation patterns, histone modifications, and microRNA expression.

    “Regarding epigenetic mechanisms, vitamin D, through its interaction with the vitamin D receptor (VDR), can modulate the activity of chromatin-modifying enzymes, including DNA methyltransferases (DNMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs).”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [134]

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  • VDR can be found in a multitude of tissues and regulates the immune system, strengthens innate immunity and suppresses adaptive immunity, decreases infection risk, protects against autoimmune diseases, reduces respiratory infections, reduces cardiovascular diseases and hypertension, prevents cancer through antiproliferative and antineoplastic functions, and stimulates insulin production frompancre

    “VDR can be found in a multitude of tissues and performs the following actions: it regulates the immune system, particularly strengthening innate immunity and suppressing adaptive immunity, decreases infection risk, protects against autoimmune diseases, reduces respiratory infections, reduces cardiovascular diseases and hypertension, prevents cancer through antiproliferative and antineoplastic”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [134]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Vitamin D is essential for human health and is mainly involved in calcium metabolism, particularly responsible for calcium and phosphate homeostasis by acting on the kidney, intestine and bone tissue.

    “Vitamin D is a micronutrient essential for human health and is mainly involved in calcium metabolism, particularly responsible for calcium and phosphate homeostasis by acting on the kidney, intestine and bone tissue.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [134]

    The Introduction (page not provided) calls vitamin D essential for health and says its active metabolite enables calcium and phosphate absorption from the intestine and bone formation. The paper also identifies calcium regulation as a classical action, but the passages do not support the claim that vitamin D acts on the kidney to maintain calcium and phosphate homeostasis. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Vitamin D and calcium are tightly interdependent, as vitamin D is essential for intestinal calcium absorption and skeletal mineralization; inadequate vitamin D status can impair calcium utilization despite sufficient intake.

    “Similarly, vitamin D and calcium are tightly interdependent, as vitamin D is essential for intestinal calcium absorption and skeletal mineralization; inadequate vitamin D status can impair calcium utilization despite sufficient intake [134].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [134]

    The Introduction (page not provided) says the active vitamin D metabolite is essential for intestinal calcium and phosphate absorption and hence for bone formation; it also links severe vitamin D deficiency to rickets. This supports the absorption and skeletal portions of the claim, but the paper does not address whether calcium utilization is impaired despite sufficient calcium intake. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Carlberg, C., & Campbell, M. J.
Affiliations
  • University of Eastern Finland (FI)
  • Roswell Park Comprehensive Cancer Center (US)
Corresponding author
Carlberg, Carsten
ORCID
Venue
Steroids
Publisher
Elsevier BV
Published
2013-02
Volume
78
Issue
2
Pages
127-136
ISSN
0039-128X (ISSN-L)
DOI
10.1016/j.steroids.2012.10.019
PMC
PMC4668715
OpenAlex
W1964335024
Cited by
293
References
10
Citations by year
2026: 18 · 2025: 19 · 2024: 13 · 2023: 21 · 2022: 24 · 2021: 13 · 2020: 24 · 2019: 23 · 2018: 24 · 2017: 26 · 2016: 19 · 2015: 29 · 2014: 27 · 2013: 13
FWCI
3.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Steroids (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Academy of Finland
  • Juselius Foundation
  • Biotechnology and Biological Sciences Research Council (UK)
  • National Institute of Health (R01 CA095367-06, 2R01-CA-095045-06)
  • NCI Cancer Center Support
  • NucSys
  • CanSys
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
vitamin D receptor, 1,25-dihydroxyvitamin D3, vitamin D signaling, transcription factors, nuclear receptor superfamily, chromatin binding, DNA binding modes, chromatin interactions, regulatory networks, calcium and phosphorus homeostasis, bone formation, immune function
MeSH terms
Animals, Base Sequence, DNA, Humans, Models, Biological, Molecular Sequence Data, Protein Binding, Signal Transduction, Genome, Receptors, Calcitriol

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