Genome-wide analysis of transcription factor binding sites during somatic cell reprogramming

We report that Zic3 and Esrrb synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. By ChIP-seq analysis, we reveal that Zic3 recruits Esrrb to its own binding sites, some of which are proximal to glycolysis-related genes, thereby cooperatively upregulating these genes to activate glycolytic metabolism, and that Esrrb binds to genes related to mitochondrial oxidative phosphorylation. Therefore, our study suggests that Zic3 and Esrrb activate pluripotency gene network by regulating the balance of metabolic pathways. Overall design: Examination of binding of 2 different transcription factors in 4 different conditions