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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1583-1587 |
| Number of pages | 5 |
| Journal | Journal of Lipid Research |
| Volume | 47 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2006 |
| Externally published | Yes |
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Keywords
- Conserved elements
- PACM
- Peroxisome proliferator-activated receptor
- Target genes
ASJC Scopus subject areas
- Endocrinology
Cite this
Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics. / Lemay, Danielle G.; Hwang, Daniel H.
In: Journal of Lipid Research, Vol. 47, No. 7, 2006, p. 1583-1587.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics
AU - Lemay, Danielle G.
AU - Hwang, Daniel H.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Conserved elements
KW - PACM
KW - Peroxisome proliferator-activated receptor
KW - Target genes
UR - http://www.scopus.com/inward/record.url?scp=33746080426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746080426&partnerID=8YFLogxK
U2 - 10.1194/jlr.M500504-JLR200
DO - 10.1194/jlr.M500504-JLR200
M3 - Article
C2 - 16585784
AN - SCOPUS:33746080426
VL - 47
SP - 1583
EP - 1587
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 7
ER -