Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements.
Genome Biol
; 15(4): R63, 2014 Apr 10.
Article
in En
| MEDLINE
| ID: mdl-24721177
ABSTRACT
BACKGROUND:
Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated.RESULTS:
We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) ß/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPARß/δ agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements.CONCLUSIONS:
To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Response Elements
/
Angiopoietins
/
PPAR-beta
/
PPAR delta
/
Hypoxia-Inducible Factor 1, alpha Subunit
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Genome Biol
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2014
Type:
Article