“…Classical genetics approaches have provided evidence of redundant, additive, and synergistic enhancer relationships at a handful of loci (Banerji et al, 1983; Banerji et al, 1981; Bender et al, 2012; Blasquez et al, 1992; de Villiers and Schaffner, 1981; Fujioka et al, 1999; Fulton and van Ness, 1994; Guo et al, 2012; Hong et al, 2008; Kehayova et al, 2011; Lam et al, 2015; Montavon et al, 2011; Perry et al, 2010; Small et al, 1992; Stern and Frankel, 2013). For example, two enhancers regulating Pomc are both necessary in the mouse embryo, indicating a synergistic relationship, while the enhancers contribute additively to Pomc expression in adult mice (Lam et al, 2015).…”