Combinatorial Binding in Human and Mouse Embryonic Stem Cells Identifies Conserved Enhancers Active in Early Embryonic Development
(A) Bars indicate the fraction of loci where binding of Nanog, Sox2, Oct4 and CTCF can be observed at the orthologous locus in mouse ES cells for all combinations of OCT4, SOX2 and NANOG in human ES cells discriminated by developmental activity as indicated by the boxes below. Dark boxes indicate “AND” relation, light grey boxes with “v” indicate “OR” relation, “?” indicates no restriction. Combinatorial binding events at developmentally active enhancers show the highest levels of binding conservation between mouse and human ES cells (>50%). (B) The fractions of binding combinations in mES cells at conserved loci (for all combinations indicated by the boxes above). The majority of conserved binding events at developmentally active enhancers where OCT4, SOX2 and NANOG bind simultaneously show combinatorial binding of Oct4, Sox2 and Nanog in mouse ES cells. (C) The fraction of proximal and distant binding sites for conserved and non-conserved binding events (split up according to the combinations of binding as indicated by the boxes above). The majority of conserved binding events are distant regulatory elements.