Project description:Previously published data suggested some redundant functions between HDAC1 and HDAC2 in mouse. To test this hypothesis, we used microarrays to have a genome wide analysis at the transcription level of primary MEFs lacking HDAC1, HDAC2. MEF HDAC1 F/F were were transduced with two different retroviruses: one virus expresses the Tamoxifen-inducible cre recombinase Cre-ERT2 and the second virus expresses either a small hairpin micro-RNA against HDAC2 or a scrambled version. HDAC1F/F MEFs expressing either a scrambled micro-RNA or a micro-RNA against HDAC2 can be induced by addition of Tamoxifen to delete HDAC1, thereby generating four different genotypes: WT, HDAC1 KO, HDAC2 knockdown (Kd) and HDAC1/2 KO/Kd.
Project description:Previously published data suggested some redundant functions between HDAC1 and HDAC2 in mouse. To test this hypothesis, we used microarrays to have a genome wide analysis at the transcription level of primary MEFs lacking HDAC1, HDAC2.
Project description:We have performed quantitative proteomic TandemMassTag to investigate proteomic changes after deletion of epigenetic eraser genes Hdac1 and Hdac2 in intestinal epithelial cells. 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 specific IEC function of HDAC1 and HDAC2, we have performed transcriptomic and quantitative proteomic approaches on IEC deficient in Hdac1 and 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.
Project description: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.
Project description: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.
Project description:In this study, we investigated the role of HDAC1 and HDAC2 in the developing mouse brain. We found that the removal of HDAC1 and HDAC2 caused severe malformation. To examine the molecular mechanisms underlying the cortical malformation, we examined the transcriptome in both WT and HDAC1/2 deficient brains. We found that many genes that are associated with transcription were misregulated in HDAC1 and HDAC2 mutant brains. This result provides a resource for studying gene expression controlled by HDAC1 and HDAC2.