Evidence map›Paper›PMID 26504088›Full record

ArticleThe Journal of biological chemistry2015

Mechanisms of Enhancer-mediated Hormonal Control of Vitamin D Receptor Gene Expression in Target Cells.

Seong Min Lee, Mark B Meyer, Nancy A Benkusky, Charles A O'Brien, J Wesley Pike

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  13. The impact of VDR expression and regulation in vivo.The Journal of steroid biochemistry and molecular biology · 2018
    Article
  14. Biology and Mechanisms of Action of the Vitamin D Hormone.Endocrinology and metabolism clinics of North America · 2017
    Review
  15. Article
  16. Review
  17. Article
  18. Review
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

5 authors at 2 institutions in 1 country.

Seong Min LeeFrom the Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 and.
Mark B MeyerFrom the Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 and.
Nancy A BenkuskyFrom the Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 and.
Charles A O'Brienthe Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
J Wesley PikeFrom the Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 and pike@biochem.wisc.edu.
University of Wisconsin–Madison · USUniversity of Arkansas for Medical Sciences · US

Funding

TRANSGENIC MOUSE COREP01AG013918 · NIA · UNIV OF ARKANSAS FOR MED SCIS · PI O'BRIEN, CHARLES A · 1996 to 2016
$25.7M
DOMINICA DIABETES AND HYPERTENSION STUDYR21DK045173 · NIDDK · CHARLES R. DREW UNIVERSITY OF MED &SCI · PI GRIM, CLARENCE E · 1992 to 1992
–
NIA NIH HHS P01 AG013918NIDDK NIH HHS DK-45173
6 · The paper itself

Abstract

The biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR), whose expression in bone cells is regulated positively by 1,25(OH)2D3, retinoic acid, and parathyroid hormone through both intergenic and intronic enhancers. In this report, we used ChIP-sequencing analysis to confirm the presence of these Vdr gene enhancers in mesenchyme-derived bone cells and to describe the epigenetic histone landscape that spans the Vdr locus. Using bacterial artificial chromosome-minigene stable cell lines, CRISPR/Cas9 enhancer-deleted daughter cell lines, transient transfection/mutagenesis analyses, and transgenic mice, we confirmed the functionality of these bone cell enhancers in vivo as well as in vitro. We also identified VDR-binding sites across the Vdr gene locus in kidney and intestine using ChIP-sequencing analysis, revealing that only one of the bone cell-type enhancers bound VDR in kidney tissue, and none were occupied by the VDR in the intestine, consistent with weak or absent regulation by the 1,25(OH)2D3 hormone in these tissues, respectively. However, a number of additional sites of VDR binding unique to either kidney or intestine were present further upstream of the Vdr gene, suggesting the potential for alternative regulatory loci. Importantly, virtually all of these regions retained histone signatures consistent with those of enhancers and exhibited unique DNase I hypersensitivity profiles that reflected the potential for chromatin access. These studies define mechanisms associated with hormonal regulation of the Vdr and hint at the differential nature of VDR binding activity at the Vdr gene in different primary target tissues in vivo.

Indexed as

AnimalsCalcitriolCell LineEnhancer Elements, GeneticGene Expression RegulationHormonesMiceMice, TransgenicReceptors, CalcitriolCalcitriolHormonesReceptors, Calcitriol1,25(OH)2D3 regulated Vdr gene expressionautoregulationChIP-sequencing (ChIP-seq)gene transcriptiontranscription enhancertranscription regulationVDR regulated enhancersvitamin D

Identifiers

PMID26504088
PMCPMC4683277
OpenAlexW2135553186

What OpenQuestion holds

Textmetadata
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.