Schematic diagram of synergistic transcription induction mediated by spatial proximity. Upper part shows the ANGPTL4 locus, including the HRE, TSS, and PPRE. PPARβ/δ sits at the PPRE before stimulation. Left: under hypoxia, acetyltransferases approach the HRE locus by virtue of HIF1α binding to the HRE. ANGPTL4 assumes a loop formation in order to bring the HRE closer to the PPRE. Although the PPRE is not a direct target of HIF1α, this conformation causes acetylation of the PPRE. Right: under PPAR ligand (agonist) stimulation, PPARβ/δ's location does not change but it is chemically modified to the active form. Presumably by virtue of a cofactor of PPAR, the PPRE comes closer to the HRE, resulting in acetylation of the HRE. Center: under dual stimulation, the HRE and PPRE move closer to each other, causing additive acetylation of both regions, and increased amounts of Pol II might be loaded at the TSS, possibly resulting in synergistic transcription activation and crosstalk.