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Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements

2014; BioMed Central; Volume: 15; Issue: 4 Linguagem: Inglês

10.1186/gb-2014-15-4-r63

1474-760X

Tsuyoshi Inoue, Takahide Kohro, Toshiya Tanaka, Yasuharu Kanki, Guoliang Li, Huay-Mei Poh, Imari Mimura, Mika Kobayashi, Akashi Taguchi, Takashi Maejima, Jun‐ichi Suehiro, Akira Sugiyama, Kiyomi Kaneki, Hirofumi Aruga, Shoulian Dong, Junko Stevens, Shogo Yamamoto, Shuichi Tsutsumi, Toshiro Fujita, Xiaoan Ruan, Hiroyuki Aburatani, Masaomi Nangaku, Yijun Ruan, Tatsuhiko Kodama, Youichiro Wada,

Peroxisome Proliferator-Activated Receptors

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.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) β/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, PPARβ/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.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.