PGC-1alpha induces dynamic protein interactions on the ERRalpha gene multi-hormone response element nucleosome in kidney cells.
ERR (oestrogen-related receptor)-alpha modulates the oestrogen signalling pathway and regulates genes participating in the physiological energy balance programme. Oestrogen and PGC-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha), the master regulator of the energy homoeostasis programme, both regulate the expression of ERRalpha through the MHRE (multi-hormone response element) of the ERRalpha gene. Although ... the molecular mechanism of oestrogen action on ERRalpha regulation is well characterized, the mechanism of PGC-1alpha induction is unclear. In this study, we examine chromatin structural changes and protein interactions at the MHRE nucleosome in response to PGC-1alpha expression in HK2 human kidney cells. We mapped the nucleosome positions of the ERRalpha gene promoter and examined the changes of histone acetylation in response to PGC-1alpha expression. The interactions of DNA-binding proteins, ERRalpha and ERRgamma, co-activators {CBP [CREB (cAMP-response-element-binding protein)-binding protein], p300, PCAF (p300/CBP-associated 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-1alpha expression in the HK2 cells. We found a dynamic cyclic interaction of these proteins shortly after PGC-1alpha 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 ERRgamma was involved in the initial phase, but not in the later phase, of PGC-1alpha-induced ERRalpha expression.
Mesh Terms:
Animals, Base Sequence, Cell Line, Chromatin, Gene Expression Regulation, Heat-Shock Proteins, Homeostasis, Humans, Kidney, Molecular Sequence Data, Nucleosomes, Promoter Regions, Genetic, RNA Interference, RNA Polymerase II, Receptors, Estrogen, Sequence Alignment, Transcription Factors
Animals, Base Sequence, Cell Line, Chromatin, Gene Expression Regulation, Heat-Shock Proteins, Homeostasis, Humans, Kidney, Molecular Sequence Data, Nucleosomes, Promoter Regions, Genetic, RNA Interference, RNA Polymerase II, Receptors, Estrogen, Sequence Alignment, Transcription Factors
Biochem. J.
Date: Dec. 15, 2008
PubMed ID: 18673300
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