Regulation of novel transcripts by ablation and overexpression of PGC-1α in vivo. Expression of putative transcriptional targets of PGC-1α was analyzed by qRT-PCR in cortical homogenates of four mouse lines. A, Complete germline knock-out of PGC-1α significantly decreased expression of the neuron-specific genes PV, Syt2, Cplx1, and Nefh and the metabolism-related genes Phyh, Inpp5j, Nceh1, Ak1, Atp5o, and Atp5a1. B, Incomplete germline deletion in which the biologically active N terminus of PGC-1α is still present significantly decreased neuron-specific but not metabolism-related transcripts. C, Conditional deletion of PGC-1α in the CNS recapitulated the transcriptional changes in the complete germline knock-out. D, Acute overexpression of PGC-1α in the cortex significantly increased the expression of all novel PGC-1α-dependent genes. Numbers per group are indicated on the bar histograms. *p < 0.05; ** p < 0.005; ***p < 0.0005, two-tailed t tests followed by Bonferroni's correction for multiple testing (A) and one-tailed t tests based on a priori hypotheses based on A (B–D). Data are presented as mean ± SEM.