Evidence map›Paper›PMID 19237542›Full record

ArticleThe Journal of biological chemistry2009

Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface.

Boris Novakovic, Mandy Sibson, Hong Kiat Ng, Ursula Manuelpillai, Vardhman Rakyan, Thomas Down, Stephan Beck, Thierry Fournier, Danielle Evain-Brion, Eva Dimitriadis and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 2 pooled it
16.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 235 citations in OpenAlex.

  1. Effect of epigenetics on vitamin D levels: a systematic review until December 2020.Archives of public health = Archives belges de sante publique · 2023
    Pooled it
  2. Pooled it
  3. Trial
  4. Effects of Maternal Vitamin D Supplementation on the Maternal and Infant Epigenome.Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine · 2018
    Trial
  5. Trial
  6. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2011
    Trial
  7. Article
  8. Review
  9. Article
  10. Article
  11. Nutraceuticals in Pregnancy: A Special Focus on Probiotics.International journal of molecular sciences · 2024
    Review
  12. Review
  13. Article
  14. Review
  15. Policing Cancer: Vitamin D Arrests the Cell Cycle.International journal of molecular sciences · 2020
    Review
  16. Vitamin D deficiency 2.0: an update on the current status worldwide.European journal of clinical nutrition · 2020
    Review
  17. Article
  18. Review
  19. Article
  20. Article

35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 3 countries.

Boris NovakovicDevelopmental Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, and Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia.
Mandy Sibson
Hong Kiat Ng
Ursula Manuelpillai
Vardhman Rakyan
Thomas Down
Stephan Beck
Thierry Fournier
Danielle Evain-Brion
Eva Dimitriadis
Jeffrey M Craig
Ruth Morley
Richard Saffery
Royal Children's Hospital · AUDélégation Paris 5 · FRInstitute of Structural and Molecular Biology · GBMonash University · AU

Funding

Wellcome Trust 084071
6 · The paper itself

Abstract

Plasma concentrations of biologically active vitamin D (1,25-(OH)(2)D) are tightly controlled via feedback regulation of renal 1alpha-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)(2)D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitamin D deregulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface.

Indexed as

DNA MethylationFeedback, PhysiologicalHomeostasisMaternal-Fetal Exchange25-Hydroxyvitamin D3 1-alpha-HydroxylaseAnimalsCalcitriolCell Line, TumorChoriocarcinomaCpG IslandsFemaleHumansMammalsOrgan SpecificityPlacentaPre-Eclampsia25-Hydroxyvitamin D3 1-alpha-HydroxylaseCalcitriolCYP24A1 protein, humanCyp24a1 protein, mouseReceptors, CalcitriolSteroid HydroxylasesVitamin DVitamin D3 24-Hydroxylase

Identifiers

PMID19237542
PMCPMC2685665
OpenAlexW2026231412

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.