An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA and protein synthesis. However, the which such “dimensions” coordinate cell currently poorly understood. Here we quantified multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses expression subsequent Esrrb or Nanog, indicated system interlocked feed-forward loops involving both factors, plays central part regulating timing mESC decisions. Taken together, our meta-analyses support hierarchical model is maintained an Oct4-Sox2 module, while differentiation regulated Nanog-Esrrb module.