Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics
Open accessAbstract
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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The PPAR-RXR dimer binds peroxisome proliferator response elements (PPRE) to activate transcription of ATP-binding cassette (ABC) family genes and genes involved in fatty acid scavenging and lipid metabolism.
“The PPAR-RXR dimer binds peroxisome proliferator response elements (PPRE) to activate the transcription of genes within the ATP-binding cassette (ABC) family and genes involved in FA scavenging and lipid metabolism [50,51,76,79].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [50]
The Abstract states that PPARs bind PPREs in regulatory regions of target genes, and the Discussion’s Table 1 lists fatty-acid and lipid metabolism among the biological processes of predicted targets. The paper does not establish activation of ABC-family or fatty-acid-scavenging genes; the Discussion also says individual predicted targets require experimental verification. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPPAR agonists protect against neuronal death and neuroinflammation and promote CNS repair.
“PPAR agonists have been shown to protect against neuronal death and neuroinflammation, and also to promote CNS repair [50,51].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [50]
The Abstract describes a genome-wide search for PPAR target genes, and the Discussion addresses immune-related gene terms and DNA damage responses. Neither section addresses whether PPAR agonists prevent neuronal death or neuroinflammation or promote CNS repair. Searches for neuronal death, neuroinflammation, CNS repair, and related terms found no supporting passage in our copy. (LLM, conf=0.75)
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- Authors
- Lemay, D. G., & Hwang, D. H.
- Affiliations
- Agricultural Research Service (US)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 47
- Issue
- 7
- Pages
- 1583-1587
- ISSN
- 0022-2275 (ISSN-L)
- 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
- 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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