Schematics show time lines for topical application of Romidepsin or vehicle to dorsal paw skin starting at P53 (both diagrams) and high-dose oral doxycycline treatment starting at P49 (right diagram). All samples were analyzed at P57. (a,b,i,j,a’,b’,i’,j’) Histology of dorsal paw skin of the indicated genotypes following treatment with vehicle (DMSO) or Romidepsin as indicated. (c-f, k-n, c’-f’, k’-n’) IF for the indicated proteins in dorsal paw skin of the indicated genotypes following vehicle or Romidepsin treatment. (g,h,o,p,g’,h’,o’,p’) TUNEL assay for the genotypes indicated following vehicle or Romidepsin treatment. Arrows in (h,h’) indicate apoptotic cells. (q) Quantitation of Ki-67-positive IFE basal cells in control or p16-null dorsal paw IFE treated with vehicle or Romidepsin. (q’) Quantitation of Ki-67-positive basal cells in GLI2ΔN-expressing dorsal paw IFE with or without p16-deletion following treatment with vehicle or Romidepsin; n=4 mice of each genotype analyzed. P-values calculated with two-tailed Student’s t-test; error bars indicate SEM. Scale bars: 25μm (a,b,i,j,a’,b’,i′,j’), 50μm (c-h, k-p, c’-h’, k’-p’).