Evidence map›Paper›PMID 20631054›Full record

ArticleMolecular pharmacology2010

Role of epigenetic mechanisms in differential regulation of the dioxin-inducible human CYP1A1 and CYP1B1 genes.

Sudheer R Beedanagari, Robert T Taylor, Peter Bui, Feng Wang, Derek W Nickerson, Oliver Hankinson

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

41 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. The aryl hydrocarbon receptor: a new frontier in male reproductive system.Reproductive biology and endocrinology : RB&E · 2025
    Review
  3. Insights intoLife (Basel, Switzerland) · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. β-naphthoflavone-induced upregulation ofExperimental and therapeutic medicine · 2021
    Article
  11. Article
  12. Review
  13. Article
  14. Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020
    Review
  15. Article
  16. Multigenerational and Transgenerational Effects of Dioxins.International journal of molecular sciences · 2019
    Review
  17. TCDD Toxicity Mediated by Epigenetic Mechanisms.International journal of molecular sciences · 2018
    Review
  18. Article
  19. Article
  20. Article
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

6 authors at 2 institutions in 1 country.

Sudheer R BeedanagariDepartmental of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, 650 Charles Young Drive, Los Angeles, CA 90095, USA.
Robert T Taylor
Peter Bui
Feng Wang
Derek W Nickerson
Oliver Hankinson
University of California, Los Angeles · USLa Roche College · US

Funding

Training in Molecular ToxicologyT32ES015457 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ALLARD, PATRICK, HANKINSON, OLIVER NMN · 2008 to 2025
$4.0M
CARCINOGEN ACTIVATION AND SCREENING IN VARIANT CELLSR01CA028868 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HANKINSON, OLIVER NMN · 1985 to 2010
$3.6M
NCI NIH HHS R01 CA028868NCI NIH HHS R01-CA28868NIEHS NIH HHS T32 ES015457NIEHS NIH HHS T32-ES015457
6 · The paper itself

Abstract

The aryl hydrocarbon receptor (AhR) mediates induction of CYP1A1 and CYP1B1 by 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (dioxin) via binding to xenobiotic-responsive elements (XREs) in their enhancer regions. CYP1A1 and CYPIB1 were both inducible by dioxin in human MCF-7 cells. However, only CYP1A1 was inducible in human HepG2 cells. Further experiments focused on providing an explanation for this last observation. Dioxin induced the recruitment of AHR and the transcriptional coactivators p300 and p300/cAMP response element-binding protein binding protein-associated factor (PCAF) to the CYP1B1 enhancer in HepG2 cells but failed to induce recruitment of RNA polymerase II (polII) or the TATA binding protein (TBP) and acetylations of histones 3 and 4 or methylation of histone 3 at the promoter. Because p300 was required for dioxin induction of the aforementioned histone modifications at the CYP1B1 promoter and for induction of CYP1B1 transcription (in MCF-7 cells), the recruitments of p300 and AhR, although necessary, are not sufficient for eliciting the above responses to dioxin. Cytosine residues within CpG dinucleotides at the enhancer, including those within the XREs, were partially methylated, whereas those at the promoter were fully methylated. Treatment of HepG2 cells with 5-aza-2'-deoxycytidine led to partial demethylation of the promoter, restored polII and TBP binding, and CYP1B1 inducibility. Thus, the deficiency of CYP1B1 induction in HepG2 cells is ascribable to cytosine methylation at the promoter, which prevents recruitment of TBP and polII. It is noteworthy that our data indicate that stable recruitment of p300 and PCAF to the CYP1B1 gene does not require their tethering to the promoter and to the enhancer.

Indexed as

Gene Expression Regulation, EnzymologicAryl Hydrocarbon HydroxylasesCell Line, TumorCytochrome P-450 CYP1A1Cytochrome P-450 CYP1B1Cytochrome P-450 Enzyme SystemDioxinsEnzyme InductionEpigenesis, GeneticHep G2 CellsHumansPolychlorinated DibenzodioxinsAryl Hydrocarbon HydroxylasesCYP1B1 protein, humanCytochrome P-450 CYP1A1Cytochrome P-450 CYP1B1Cytochrome P-450 Enzyme SystemDioxinsPolychlorinated Dibenzodioxins

Identifiers

PMID20631054
PMCPMC2981391
OpenAlexW2098919158

What OpenQuestion holds

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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.