Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements
| Autor: | Kiyomi Kaneki, Shuichi Tsutsumi, Takashi Maejima, Yijun Ruan, Imari Mimura, Akira Sugiyama, Yasuharu Kanki, Jun-ichi Suehiro, Shoulian Dong, Toshiya Tanaka, Xiaoan Ruan, Tatsuhiko Kodama, Junko F Stevens, Shogo Yamamoto, Hiroyuki Aburatani, Guoliang Li, Akashi Taguchi, Mika Kobayashi, Youichiro Wada, Takahide Kohro, Masaomi Nangaku, Toshiro Fujita, Huay-Mei Poh, Tsuyoshi Inoue, Hirofumi Aruga |
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| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
Genetics Conformational change Research Peroxisome proliferator-activated receptor Biology Chromatin Assembly and Disassembly Hypoxia-Inducible Factor 1 alpha Subunit Response Elements Cell Hypoxia Chromatin Cell biology Chromosome conformation capture chemistry Transcription (biology) Gene expression Human Umbilical Vein Endothelial Cells Transcriptional regulation Angiopoietin-Like Protein 4 Humans PPAR delta Enhancer Angiopoietins PPAR-beta Transcription factor |
| Zdroj: | Genome Biology |
| ISSN: | 1465-6906 |
| Popis: | 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) 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. 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. |
| Databáze: | OpenAIRE |
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