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[摘要]：ERR (oestrogen-related receptor)-alpha modulates the oestrogen signalling pathway and regulates genes participating in the physiological energy balance programme. Oestrogen and PGC-1 alpha (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha), the master regulator of the energy homoeostasis programme, both regulate the expression of ERR alpha through the MHRE (multi-hormone response element) of the ERR alpha gene. Although the molecular mechanism of oestrogen action on ERR alpha regulation is well characterized, the mechanism of PGC-1 alpha induction is unclear. In this study, we examine chromatin Structural changes and protein interactions at the MHRE nucleosome in response to PGC-1 alpha expression in HK2 human kidney cells. We mapped the nucleosome positions of the ERR alpha gene promoter and examined the changes of historic acetylation in response to PGC-1 alpha expression. The interactions of DNA-binding proteins, ERR alpha and ERR gamma. co-activators {CBP [CREB (cAMP-response-element-binding protein)-binding protein], p300, PCAF (p300/CBP-associated factor)}, co-repressor [RIP140 (receptor-interacting protein of 140kDa)] and RNA polymerase II at the MHRE nucleosome region were investigated over time before and after PGC-1 alpha expression in the HK2 cells. We found a dynamic cyclic interaction of these proteins shortly after PGC-1 alpha 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 ERR gamma was involved in the initial phase, but not in the later phase, of PGC-1 alpha-induced ERR alpha expression. |
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