Evidence map›Paper›PMID 31040347›Full record

ArticleScientific reports2019

Transcriptomic profiling identifies novel mechanisms of transcriptional regulation of the cytochrome P450 (Cyp)3a11 gene.

Guncha Taneja, Suman Maity, Weiwu Jiang, Bhagavatula Moorthy, Cristian Coarfa, Romi Ghose

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

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  8. Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells.Journal of experimental & clinical cancer research : CR · 2020
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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 3 institutions in 1 country.

Guncha TanejaDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, 4849 Calhoun Rd., Houston, TX, 77204, USA.
Suman MaityAdvanced Technology Cores, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Weiwu JiangDepartment of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, Suite 530, Houston, TX, 77030, USA.
Bhagavatula MoorthyDepartment of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, Suite 530, Houston, TX, 77030, USA. bmoorthy@bcm.edu.
Cristian CoarfaDan L Duncan Comprehensive Cancer Center, Center for Precision Environmental Health, Molecular and Cellular Biology Department, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. coarfa@bcm.edu.
Romi GhoseDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, 4849 Calhoun Rd., Houston, TX, 77204, USA. rghose@central.uh.edu.
Baylor College of Medicine · USUniversity of Houston · USTexas Children's Hospital · US

Funding

Project 5: Pyolytic conversion of PAHs in contaminated sediments into char to eliminate toxicity and enhance soil fertilityP42ES027725 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI BHAGAVATULA MOORTHY · 2020 to 2026
$17.8M
Translational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Casey W Wright · 2019 to 2026
$14.7M
MOLECULAR MECHANISMS OF CYTOCHROME P4501A1 EXPRESSIONR01ES009132 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI MOORTHY, BHAGAVATULA · 1998 to 2017
$3.8M
Mechanistic role of P4501 enzymes in the prevention of PAH carcinogenesis by omega 3 fatty acidsR01ES029382 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI MOORTHY, BHAGAVATULA · 2018 to 2022
$2.3M
Supplement2: Mechanistic Roles of Cytochrome P4501A Enzymes in Hyperoxic Lung InjuryR01HL129794 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MOORTHY, BHAGAVATULA · 2016 to 2019
$2.2M
Epigenetic variation at metastable epialleles: Effects on human obesityR01DK111522 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI COARFA, CRISTIAN, WATERLAND, ROBERT A · 2017 to 2020
$1.8M
Novel in vivo regulatory mechanisms of human CYP3A4R21DA035751 · NIDA · UNIVERSITY OF HOUSTON · PI GHOSE, ROMI, MOORTHY, BHAGAVATULA · 2014 to 2015
$428k
NHLBI NIH HHS R01 HL129794NIDA NIH HHS R21 DA035751NIDDK NIH HHS R01 DK111522NIEHS NIH HHS P30 ES030285NIEHS NIH HHS P42 ES027725NIEHS NIH HHS R01 ES009132NIEHS NIH HHS R01 ES029382
6 · The paper itself

Abstract

Cytochrome P450 (CYP)3A is the most abundant CYP enzyme in the human liver, and a functional impairment of this enzyme leads to unanticipated adverse reactions and therapeutic failures; these reactions result in the early termination of drug development or the withdrawal of drugs from the market. The transcriptional regulation mechanism of the Cyp3a gene is not fully understood and requires a thorough investigation. We mapped the transcriptome of the Cyp3a gene in a mouse model. The Cyp3a gene was induced using the mPXR activator pregnenolone-16alpha-carbonitrile (PCN) and was subsequently downregulated using lipopolysaccharide (LPS). Our objective was to identify the transcription factors (TFs), epigenetic modulators and molecular pathways that are enriched or repressed by PCN and LPS based on a gene set enrichment analysis. Our analysis shows that 113 genes were significantly upregulated (by at least 1.5-fold) with PCN treatment, and that 834 genes were significantly downregulated (by at least 1.5-fold) with LPS treatment. Additionally, the targets of the 536 transcription factors were enriched by a combined treatment of PCN and LPS, and among these, 285 were found to have binding sites on Cyp3a11. Moreover, the repressed targets of the epigenetic markers HDAC1, HDAC3 and EZH2 were further suppressed by LPS treatment and were enhanced by PCN treatment. By identifying and contrasting the transcriptional regulators that are altered by PCN and LPS, our study provides novel insights into the transcriptional regulation of CYP3A in the liver.

Indexed as

Gene Expression ProfilingGene Expression RegulationTranscriptomeAnimalsComputational BiologyCytochrome P-450 CYP3AEnzyme ActivationEpigenesis, GeneticMembrane ProteinsMiceSignal TransductionTranscription FactorsCyp3a11 protein, mouseCytochrome P-450 CYP3AMembrane ProteinsTranscription Factors

Identifiers

PMID31040347
PMCPMC6491424
OpenAlexW2943448932

What OpenQuestion holds

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LicenceCC BY
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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.