Title
Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements.
Document Type
Article
Publication Date
4-10-2014
JAX Source
Genome Biol 2014 Apr 10; 15(4):R63.
PMID
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) beta/delta 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, PPARbeta/delta 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.
Genome Biol 2014 Apr 10; 15(4):R63.
Recommended Citation
Inoue, Tsuyoshi; Kohro, Takahide; Tanaka, Toshiya; Kanki, Yasuharu; Li, Guoliang; Poh, Huay-Mei; Mimura, Imari; Kobayashi, Mika; Taguchi, Akashi; Maejima, Takashi; Suehiro, Jun-Ichi; Sugiyama, Akira; Kaneki, Kiyomi; Aruga, Hirofumi; Dong, Shoulian; Stevens, Junko F; Yamamoto, Shogo; Tsutsumi, Shuichi; Fujita, Toshiro; Ruan, Xiaoan; Aburatani, Hiroyuki; Nangaku, Masaomi; Ruan, Yijun; Kodama, Tatsuhiko; and Wada, Youichiro, "Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements." (2014). Faculty Research 2014. 92.
https://mouseion.jax.org/stfb2014/92