Figure 6.

Transcriptional regulatory circuitry of PPARGC1A and its network partners. (A) Regulator binding at the PPARGC1A locus. Signal maps are displayed for four factors that occupy PPARGC1A. Significant peaks (q < 0.01) are indicated by colored lines under each signal map. (X-axis) Chromosomal positions. Gene structure is shown to scale below the signal maps. (B) Transcriptional regulatory network diagram displaying interactions among CEBPB, ESRRA, GABP, NR3C1, HNF4A, HSF1, and PPARGC1A. (Arrows) Direct binding of one regulator to the 5′-proximal, 3′-proximal, or intragenic region of the gene encoding another regulator (or the same regulator in the case of autoregulatory loops). (C) Regulatory hierarchy among the seven regulators depicted in B. Factors are ranked first by the number of incoming network connections (“k_in”) then by the number of outgoing network connections (“k_out”) (Borneman et al. 2006). (D) Expanded transcriptional regulatory network. Additional TFs were added to the core network shown in B, represented here by the circle in the center of the diagram, if they contained four or more incoming network connections. The number of incoming connections is indicated by arrow types according to the legend. Fifteen representative TFs are shown; the complete list of 155 TFs in the expanded network and their bound regulators is available in Supplemental Table S10.