A Feed-Forward Circuit of Endogenous PGC-1α and Estrogen Related Receptor α Regulates the Neuronal Electron Transport Chain

Figure 3

PGC-1α physically associates with evolutionary conserved ERRα binding motifs in the promoters of neuronal electron transport chain genes that are dysregulated in Parkinson’s disease. (a) The VISTA plot of a 2-kb promoter region of the SDHB gene is shown with percentage identity of the human and mouse sequences. Small vertical bars indicate the location of conserved predicted ERRE binding motifs and the asterisk indicates the binding motif assayed by quantitative chromatin immunoprecipitation. (b) Quantitative chromatin immunoprecipitation (qChIP) analyses in SK-N-MC neuroblastoma cells transfected with a myc-tagged PGC-1α plasmid construct were performed. Promoter fragments for ATP5A1 (complex V), COX5B (complex IV), NDUFB5 (complex I), and SDHB (complex II) were specifically enriched in the IP fraction of PGC-1α compared to IgG control indicating PGC-1α occupancy of the conserved ERRE motifs. UCP-2, a known transcriptional target of PGC-1α  [22], was used as positive control. No PGC-1α occupancy was seen in intergenic regions lacking a predicted ERRα binding site that was included as a negative control. Quantitative PCR data were normalized to genomic DNA and visualized as percent input. denotes value ≤ 0.05.