Cited by 144Peroxisome Proliferator-Activated ReceptorsGenomics and Chromatin DynamicsNutrition, Genetics, and Disease

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Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics

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Lemay, Danielle G., Hwang, Daniel H.·2006·Journal of Lipid Research

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Abstract

Peroxisome proliferator-activated receptor (PPAR) agonists are currently used therapeutically in humans, even though many of their direct gene targets are unknown. Because PPARs can directly regulate gene expression through peroxisome proliferator response elements (PPREs), we pursued the computational prediction of PPREs on a genome-wide scale. Contrary to current hypotheses, PPREs are not isotype-specific, nor do flanking nucleotides confer additional information. However, a position weight matrix-based search for PPREs within upstream conserved elements yielded sufficient selectivity for a genome-wide search. Additionally, a novel motif occurring with greater prevalence than PPREs was revealed. Microarray and gene ontology analyses further validated our search technique and provided new functional clusters of genes that were not previously known to be directly regulated by PPARs (e.g., chromatin remodeling, DNA damage response, Wnt, and mitogen-activated protein kinase signaling). This first genome-wide library of high-confidence predicted PPAR target genes will be a valuable resource to PPAR biologists.

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Authors: Lemay, D. G., & Hwang, D. H.
Affiliations: Agricultural Research Service (US)
ORCID: Lemay, Danielle G.
Hwang, Daniel H.
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2006-07
Volume: 47
Issue: 7
Pages: 1583-1587
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.m500504-jlr200
OpenAlex: W2147427406
Cited by: 143
References: 21
Citations by year: 2026: 1 · 2025: 3 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 12 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 14
FWCI: 5.31
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5175 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: U.S. Department of Agriculture (01A095Rev)
National Institutes of Health
Agricultural Research Service
National Institute of Diabetes and Digestive and Kidney Diseases (DK-064007, R01DK064007)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords: peroxisome proliferator response element, peroxisome proliferator-activated receptors, PPAR target genes, transcription factor binding site prediction, position weight matrices, PPAR agonists, chromatin remodeling, DNA damage response, Wnt signaling, MAPK signaling
MeSH terms: Animals, DNA, Gene Expression Regulation, Humans, Gene Library, Genome, Human, Conserved Sequence, Computational Biology, Oligonucleotide Array Sequence Analysis, Genomics, Peroxisome Proliferator-Activated Receptors, Mice, Rats

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Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics

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