Promoter analysis reveals multiple M- and E-box elements upstream of the transcription start site of the CDKN2A gene isoform p16 INK4A that are conserved between human and mouse. ChIP analysis in normal human melanocytes reveals that the promoter is bound in vivo by MITF to drive p16INK4A expression. MITF-dependent expression requires an intact binding site and the DNA-binding region of MITF, and drives upregulation of p16INK4A mRNA and protein levels (Loercher et al, 2005). Ectopic expression of MITF in mouse embryonic fibroblasts causes growth inhibition, morphological changes consistent with melanocyte differentiation and an accumulation of hypophosphorylated pRB (Loercher et al, 2005). Depletion of MITF with siRNA in normal melanocytes decreased the expression of p16INK4A, caused an accumulation of hypophosphorylated pRB and promoted reentry into the cell cycle as assessed by BrdU incorporation (Loercher et al, 2005). Expression of p16INK4A is required both for cell cycle arrest as well as for the morphological changes and S100 expression, both of which are consistent with differentiation into melanocytes in these cells (Loercher et al, 2005).