The rheostat can also explain why depletion of endogenous BRN2 from different melanoma cell lines can result in different degrees of MITF reduction (Cook et al., 2005; Kundu et al., 2017; Simmons et al., 2017; Thurber et al., 2011; Wellbrock et al., 2008) or even an increase in MITF expression, as reported in 501mel cells (Goodall et al., 2008). The gene discussed is POU3F2; the disease is melanoma.