Meta-analysis of primary target genes of peroxisome proliferator-activated receptors
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BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the development of diseases, such as obesity, cardiovascular disease, type 2 diabetes and cancer. Here, an in silico screening method is presented, which incorporates experiment- and informatics-derived evidence, such as DNA-binding data of PPAR subtypes to a panel of PPAR response elements (PPREs), PPRE location relative to the transcription start site (TSS) and PPRE conservation across multiple species, for more reliable prediction of PPREs. RESULTS: In vitro binding and in vivo functionality evidence agrees with in silico predictions, validating the approach. The experimental analysis of 30 putative PPREs in eight validated PPAR target genes indicates that each gene contains at least one functional, strong PPRE that occurs without positional bias relative to the TSS. An extended analysis of the cross-species conservation of PPREs reveals limited conservation of PPRE patterns, although PPAR target genes typically contain strong or multiple medium strength PPREs. Human chromosome 19 was screened using this method, with validation of six novel PPAR target genes. CONCLUSION: An in silico screening approach is presented, which allows increased sensitivity of PPAR binding site and target gene detection.
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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 [51]
The Background (page unavailable) says PPARs bind DNA as heterodimers with RXR at PPREs to modulate target-gene transcription. The Results section on human chromosome 19 (page unavailable) identifies candidate genes involved in lipid transport and metabolism, but the copy does not establish PPRE-mediated activation of ATP-binding cassette (ABC) family genes or specifically characterize the targets as fatty-acid-scavenging genes. (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 [51]
The Background discusses PPAR ligands and their roles in metabolism, growth, and differentiation, but does not address protection from neuronal death or neuroinflammation, or CNS repair. Searches of our full-text copy for those outcomes and related nervous-system terms found no passage establishing the claim. (LLM, conf=0.73)
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Peroxisome Proliferator-activated Receptor β/δ Induces Myogenesis by Modulating Myostatin Activity
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RetractedPicrasidine N Is a Subtype-Selective PPARβ/δ Agonist
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Self-citation
- Authors
- Heinäniemi, M., Uski, J. O., Degenhardt, T., & Carlberg, C.
- Affiliations
- University of Eastern Finland (FI)
- Corresponding author
- Carlberg, Carsten
- Venue
- Genome Biology
- Published
- 2007-07-25
- Volume
- 8
- Issue
- 7
- Pages
- R147-R147
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2323243
- OpenAlex
- W2147385482
- Cited by
- 71
- References
- 79
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 8 · 2012: 6
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Academy of Finland
- Tekes
- 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 › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- peroxisome proliferator-activated receptors, PPAR target genes, PPAR response element, DNA binding site prediction, transcription start sites, cross-species conservation, chromosome 19, obesity, type 2 diabetes, cardiovascular disease, cancer
- MeSH terms
- Animals, Base Sequence, Cell Line, Chromosomes, Human, Pair 19, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Evolution, Molecular, Computational Biology, Peroxisome Proliferator-Activated Receptors, Regulatory Elements, Transcriptional, Mice
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