We have exploited organoid SILAC approaches that we have previously developed (A SILAC-Based Method for Quantitative Proteomic Analysis of Intestinal Organoids.- Gonneaud A, Jones C, Turgeon N, Lévesque D, Asselin C, Boudreau F, Boisvert FM. -Sci Rep. 2016 Nov 30;6:38195. doi: 10.1038/srep38195) to investigate proteomic changes after deletion of epigenetic eraser genes Hdac1 and Hdac2 in enteroids. Both HDAC1 and HDAC2 are epigenetic erasers that drive specific and redundant gene expression patterns, in part by removing acetyl groups on histones. Deletion of these Hdac in intestinal epithelial cell (IEC) in vivo alters intestinal homeostasis, dependent on the Hdac deleted and the level of expression of both. To determine the intrinsic specific IEC function of HDAC1 and HDAC2, we have performed transcriptomic and quantitative proteomic approaches on enteroids deficient in Hdac1 or Hdac2. We have defined changes in both mRNA and protein expression patterns affecting IEC differentiation. We have identified IEC Hdac1- and Hdac2-dependent common as well as specific pathways and biological processes. These findings uncover unrecognized similarities and differences between Hdac1 and Hdac2 in IEC.