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. Author manuscript; available in PMC: 2011 Sep 17.
Published in final edited form as: Cell. 2010 Sep 17;142(6):930–942. doi: 10.1016/j.cell.2010.08.030

Figure 7. Lsd1 represses rdh1l expression and intestinal differentiation, and a model for retinoic acid regulation of DNA methylation dynamics.

Figure 7

(A) Whole mount in situ staining for lsd1 and corest in the intestine (arrows) of apcmcr and apcwt embryos (72hpf). (B) Fold change in rdh1l expression compared to 28S levels in apcwt and apcmcr embryos injected with control/lsd1/corest Mo or treated with pargyline (to inhibit Lsd1 activity). Error bars indicate +/− SD. Lsd1 and Corest morpholino knockdown efficiency is shown in Figure S7A-B. (C) Whole mount in situ staining for fabp2 and irbp in apcmcr and apcwt embryos injected with control/lsd1/corest Mo or treated with pargyline (3mM). (D-E) Model of APC regulation of intestinal fating via retinoic acid and demethylase. APC promotes RA production by directly negatively regulating CtBP1 levels in a proteasome-dependent fashion. APC also inhibits the transcription of LSD1, CoREST, LEF1 and TLE3. LEF1 binds to the RDH promoter and recruits TLE3 (Groucho2)/CtBP1/LSD1 repressors which silence RDH expression. Retinoic acid negatively regulates demethylase components by inhibiting Pou5f1 and Cebpβ. Furthermore, regulation of demethylase components by APC is independent of β-catenin. Demethylase promotes the demethylation of key fate regulators (like aldh1a2, hoxa13a, evx1) and proliferative genes (like cyclind1 and pitx2). Fate regulators like aldh1a2 possibly help in maintaining a progenitor cell population. See also Figure S7.