Evidence map›Paper›PMID 28583088›Full record

ArticleBMC genomics2017

Uncovering the transcriptomic and epigenomic landscape of nicotinic receptor genes in non-neuronal tissues.

Bo Zhang, Pamela Madden, Junchen Gu, Xiaoyun Xing, Savita Sankar, Jennifer Flynn, Kristen Kroll, Ting Wang

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Hepatic FGF21 Deletion Improves Glucose Metabolism, Alters Lipogenic andInternational journal of molecular sciences · 2025
    Article
  2. Article
  3. Nicotinic receptors in airway disease.American journal of physiology. Lung cellular and molecular physiology · 2024
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Biliary epithelium: A neuroendocrine compartment in cholestatic liver disease.Clinics and research in hepatology and gastroenterology · 2018
    Review
  13. Article
  14. Acetylcholine nicotinic receptor subtypes in chromaffin cells.Pflugers Archiv : European journal of physiology · 2018
    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

8 authors at 2 institutions in 2 countries.

Bo ZhangCenter of Regenerative Medicine, Department of Developmental Biology, Washington University School of Medicine, Room 3212, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA. bzhang29@wustl.edu.ORCID 0000-0003-2962-5314
Pamela MaddenDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Junchen GuCenter for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, Room 5211, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Xiaoyun XingCenter for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, Room 5211, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Savita SankarCenter of Regenerative Medicine, Department of Developmental Biology, Washington University School of Medicine, Room 3212, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Jennifer FlynnCenter for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, Room 5211, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Kristen KrollCenter of Regenerative Medicine, Department of Developmental Biology, Washington University School of Medicine, Room 3212, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Ting WangCenter for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, Room 5211, 4515 McKinley Research Building, 4515 McKinley Ave, St. Louis, MO, 63110, USA. twang@genetics.wustl.edu.
Washington University in St. Louis · USCenter for Human Genetics · US

Funding

THE WASHU TARGET ENVIRONMENTAL EPIGENOMICS DATA COORDINATION CENTERU24ES026699 · NIEHS · WASHINGTON UNIVERSITY · PI WANG, TING · 2016 to 2021
$5.2M
RESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICSR25DA027995 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN, RICE, JOHN P. · 2009 to 2019
$4.3M
TRANSCRIPTIONAL REGULATION BY GEMININR01GM066815 · NIGMS · WASHINGTON UNIVERSITY · PI KROLL, KRISTEN L · 2003 to 2016
$4.2M
DECODING THE IMPACT OF TRANSPOSABLE ELEMENTS ON GENE REGULATIONR01HG007175 · NHGRI · WASHINGTON UNIVERSITY · PI WANG, TING · 2014 to 2021
$2.7M
Connecting transposable elements and regulatory innovation using ENCODE dataU01HG009391 · NHGRI · WASHINGTON UNIVERSITY · PI COHEN, BARAK A, FESCHOTTE, CEDRIC · 2017 to 2021
$2.4M
The WashU 4DN Network Data Coordination and Integration CenterU01CA200060 · NCI · WASHINGTON UNIVERSITY · PI WANG, TING · 2015 to 2019
$1.9M
ADVANCED EPI/GENOME BROWSER WITH ENHANCED VISUALIZATION AND ANALYSIS TOOLSR01HG007354 · NHGRI · WASHINGTON UNIVERSITY · PI WANG, TING · 2013 to 2016
$1.5M
CHARTING THE EPIGENOMIC LANDSCAPE OF HUMAN TRANSPOSABLE ELEMENTSR01ES024992 · NIEHS · WASHINGTON UNIVERSITY · PI WANG, TING · 2014 to 2015
$342k
NCI NIH HHS U01 CA200060NHGRI NIH HHS R01 HG007175NHGRI NIH HHS R01 HG007354NHGRI NIH HHS U01 HG009391NIDA NIH HHS R25 DA027995NIEHS NIH HHS R01 ES024992NIEHS NIH HHS U24 ES026699NIGMS NIH HHS R01 GM066815
6 · The paper itself

Abstract

backgroundNicotinic acetylcholine receptors (nAChRs) play an important role in cellular physiology and human nicotine dependence, and are closely associated with many human diseases including cancer. For example, previous studies suggest that nAChRs can re-wire gene regulatory networks in lung cancer cell lines. However, the tissue specificity of nAChRs genes and their regulation remain unexplored.

resultIn this study, we integrated data from multiple large genomic consortiums, including ENCODE, Roadmap Epigenomics, GTEx, and FANTOM, to define the transcriptomic and epigenomic landscape of all nicotinic receptor genes across many different human tissues and cell types. We found that many important nAChRs, including CHRNA3, CHRNA4, CHRNA5, and CHRNB4, exhibited strong non-neuronal tissue-specific expression patterns. CHRNA3, CHRNA5, and CHRNB4 were highly expressed in human colon and small intestine, and CHRNA4 was highly expressed in human liver. By comparing the epigenetic marks of CHRNA4 in human liver and hippocampus, we identified a novel liver-specific transcription start site (TSS) of CHRNA4. We further demonstrated that CHRNA4 was specifically transcribed in hepatocytes but not transcribed in hepatic sinusoids and stellate cells, and that transcription factors HNF4A and RXRA were likely upstream regulators of CHRNA4. Our findings suggest that CHRNA4 has distinct transcriptional regulatory mechanisms in human liver and brain, and that this tissue-specific expression pattern is evolutionarily conserved in mouse. Finally, we found that liver-specific CHRNA4 transcription was highly correlated with genes involved in the nicotine metabolism, including CYP2A6, UGT2B7, and FMO3. These genes were significantly down-regulated in liver cancer patients, whereas CHRNA4 is also significantly down-regulated in cancer-matched normal livers.

conclusionsOur results suggest important non-neuronally expressed nicotinic acetylcholine receptors in the human body. These non-neuronal expression patterns are highly tissue-specific, and are epigenetically conserved during evolution in the context of non-conserved DNA sequence.

Indexed as

EpigenomicsGene Expression ProfilingAnimalsConserved SequenceEvolution, MolecularHepatocyte Nuclear Factor 4HumansLiverMiceNicotineOrgan SpecificityPolymorphism, Single NucleotidePromoter Regions, GeneticReceptors, NicotinicRetinoid X Receptor alphaHepatocyte Nuclear Factor 4Hnf4a protein, mouseNicotineReceptors, NicotinicRetinoid X Receptor alphaCHRNA4EpigeneticsEvolutionLiverNicotinic acetylcholine receptorsTissue-specificity

Identifiers

PMID28583088
PMCPMC5460472
OpenAlexW2621995804

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Registered trials

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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.