Evidence map›Paper›PMID 22179019›Full record

ArticleArchives of biochemistry and biophysics2012

Regulation of mouse Cyp24a1 expression via promoter-proximal and downstream-distal enhancers highlights new concepts of 1,25-dihydroxyvitamin D(3) action.

J Wesley Pike, Mark B Meyer

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Archives of biochemistry and biophysics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. bioRxiv : the preprint server for biology · 2024
    Article
  5. Article
  6. Article
  7. Vitamin DInternational journal of molecular sciences · 2022
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Vitamin DBMC endocrine disorders · 2020
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

J Wesley PikeDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. pike@biochem.wisc.edu
Mark B Meyer
University of Wisconsin–Madison · US

Funding

Dynamic Mechanisms of Vitamin D-Induced Gene ExpressionR01DK072281 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI PIKE, J WESLEY · 2005 to 2012
$2.6M
Vitamin D Ligands and Regulation of Calcium HomeostasisR01DK073995 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI PIKE, J WESLEY · 2008 to 2012
$1.5M
NIDDK NIH HHS DK-072281NIDDK NIH HHS DK-073995NIDDK NIH HHS R01 DK072281NIDDK NIH HHS R01 DK073995
6 · The paper itself

Abstract

CYP24A1 functions in vitamin D target tissues to degrade 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Thus, the concentration of this enzyme and the regulation of its expression is a primary determinant of the overall biological activity of 1,25(OH)(2)D(3) within cells. The principle regulator of CYP24A1 expression is 1,25(OH)(2)D(3) itself, which functions through the vitamin D receptor to upregulate the transcriptional activity of the Cyp24a1 gene. In this report, we explore the mechanism of this regulation using recently developed ChIP-chip and ChIP-seq techniques that permit an unbiased search for enhancer elements that participate in this transcriptional control. Our studies both confirm a regulatory region defined earlier and located proximal to the transcriptional start site (TSS) of mouse Cyp24a1 (-160 and -265nt) and identify a novel intergenic region located downstream of the transcription unit that contains two enhancers (+35 and +37kb) that facilitate 1,25(OH)(2)D(3)-dependent upregulation of Cyp24a1 expression. Interestingly, while C/EBPβ also binds under basal conditions to a site located immediately upstream of the Cyp24a1 promoter (-345nt), occupancy by this factor is strikingly increased following 1,25(OH)(2)D(3) treatment. The locations and activities of these regulatory regions that mediate 1,25(OH)(2)D(3) actions were confirmed in mice in vivo. We conclude that the mechanism through which 1,25(OH)(2)D(3) induces the CYP24A1 enzyme, thereby autoregulating its own destruction, involves both promoter-proximal as well as downstream-distal enhancers. These findings highlight new concepts regarding the molecular mechanism of action of 1,25(OH)(2)D(3) and other hormonal regulators.

Indexed as

AnimalsBase SequenceCalcitriolCCAAT-Enhancer-Binding Protein-betaCell LineDNA MethylationEnhancer Elements, GeneticGene Expression RegulationGenetic LociHistonesMiceNucleotide MotifsPromoter Regions, GeneticReceptors, CalcitriolRetinoid X ReceptorsRNA Polymerase IICalcitriolCCAAT-Enhancer-Binding Protein-betaCyp24a1 protein, mouseHistonesReceptors, CalcitriolRetinoid X ReceptorsRNA Polymerase IISteroid HydroxylasesVitamin D3 24-Hydroxylase

Identifiers

PMID22179019
PMCPMC3314719
OpenAlexW2126050914

What OpenQuestion holds

Textmetadata
LicenceTDM
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.