PGC-1α induces dynamic protein interactions on the ERRα gene multi-hormone response element nucleosome in kidney cells

ERR (oestrogen-related receptor)-α modulates the oestrogen signalling pathway and regulates genes participating in the physiological energy balance programme. Oestrogen and PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α), the master regulator of the energy homoeostasis programme, both regulate the expression of ERRα through the MHRE (multihormone response element) of the ERRα gene. Although the molecular mechanism of oestrogen action on ERRα regulation is well characterized, the mechanism of PGC-1α induction is unclear. In this study, we examine chromatin structural changes and protein interactions at the MHRE nucleosome in response to PGC-1α expression in HK2 human kidney cells. We mapped the nucleosome positions of the ERRα gene promoter and examined the changes of histone acetylation in response to PGC-1α expression. The interactions of DNA-binding proteins, ERRα and ERRγ , co-activators {CBP [CREB (cAMP-response-elementbinding protein)-binding protein], p300, PCAF (p300/CBPassociated factor)}, co-repressor [RIP140 (receptor-interacting protein of 140 kDa)] and RNA polymerase II at the MHRE nucleosome region were investigated over time before and after PGC-1α expression in the HK2 cells. We found a dynamic cyclic interaction of these proteins shortly after PGC-1α expression and a slower cycling interaction, with fewer proteins involved, 20 h later. By using the siRNA (small interfering RNA) knockdown approach, we discovered that ERRγ was involved in the initial phase, but not in the later phase, of PGC-1α-induced ERRα expression.