Fibroblast histone deacetylase-1 promotes kidney interstitial fibrosis following ischemia-reperfusion injury.
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE310601 | GEO | 2025/11/24
REPOSITORIES: GEO
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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.
2021-09-09 | PXD022558 | Pride
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.
2019-11-14 | PXD011869 | Pride
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.
2019-12-31 | GSE124146 | GEO
Project description:comparative genome hybridisation of Hdac1/2 cKO lymphomas and matched normal tissue Histone deacetylases (HDACs) are epigenetic erasers of lysine-acetyl marks. Inhibition of HDACs using small molecule inhibitors (HDACi) is a potential strategy in the treatment of various diseases and is approved for treating hematological malignancies. Harnessing the therapeutic potential of HDACi requires knowledge of HDAC-function in vivo. Here, we generated a thymocyte-specific gradient of HDAC-activity using compound conditional knockout mice for Hdac1 and Hdac2. Unexpectedly, gradual loss of HDAC-activity engendered a dosage dependent accumulation of immature thymocytes and correlated with the incidence and latency of monoclonal lymphoblastic thymic lymphomas. Strikingly, complete ablation of Hdac1 and Hdac2 abrogated lymphomagenesis due to a block in early thymic development. Genomic, biochemical and functional analyses of pre-leukemic thymocytes and tumors revealed a critical role for Hdac1/Hdac2-governed HDAC-activity in regulating a p53-dependent barrier to constrain Myc-overexpressing thymocytes from progressing into lymphomas by regulating Myc-collaborating genes. One Myc-collaborating and p53-suppressing gene, Jdp2, was derepressed in an Hdac1/2-dependent manner and critical for the survival of Jdp2-overexpressing lymphoma cells. Although reduced HDAC-activity facilitates oncogenic transformation in normal cells, resulting tumor cells remain highly dependent on HDAC-activity, indicating that a critical level of Hdac1 and Hdac2 governed HDAC-activity is required for tumor maintenance. genomic DNA from LckCre+;Hdac1/2 cKO lymphomas and matched normal genomic DNA was hybridized onto a Nimblegen whole genome array
2013-01-11 | E-GEOD-43407 | biostudies-arrayexpress
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 IEC-deficient for 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 normal IEC and HDAC1/2 deleted jejunum IEC.
2020-12-31 | GSE158522 | GEO
Project description:comparative genome hybridisation of Hdac1/2 cKO lymphomas and matched normal tissue Histone deacetylases (HDACs) are epigenetic erasers of lysine-acetyl marks. Inhibition of HDACs using small molecule inhibitors (HDACi) is a potential strategy in the treatment of various diseases and is approved for treating hematological malignancies. Harnessing the therapeutic potential of HDACi requires knowledge of HDAC-function in vivo. Here, we generated a thymocyte-specific gradient of HDAC-activity using compound conditional knockout mice for Hdac1 and Hdac2. Unexpectedly, gradual loss of HDAC-activity engendered a dosage dependent accumulation of immature thymocytes and correlated with the incidence and latency of monoclonal lymphoblastic thymic lymphomas. Strikingly, complete ablation of Hdac1 and Hdac2 abrogated lymphomagenesis due to a block in early thymic development. Genomic, biochemical and functional analyses of pre-leukemic thymocytes and tumors revealed a critical role for Hdac1/Hdac2-governed HDAC-activity in regulating a p53-dependent barrier to constrain Myc-overexpressing thymocytes from progressing into lymphomas by regulating Myc-collaborating genes. One Myc-collaborating and p53-suppressing gene, Jdp2, was derepressed in an Hdac1/2-dependent manner and critical for the survival of Jdp2-overexpressing lymphoma cells. Although reduced HDAC-activity facilitates oncogenic transformation in normal cells, resulting tumor cells remain highly dependent on HDAC-activity, indicating that a critical level of Hdac1 and Hdac2 governed HDAC-activity is required for tumor maintenance.
2013-01-11 | GSE43407 | GEO
Project description:TIPARP-overexpression alter the gene expression profiles associated with remodeling of extracelluar matrix.
2023-03-01 | GSE199414 | GEO
Project description:Dynamic changes in histone acetylation patterns are mediated by the activity of histone acetyltransfereases (HATs) and histone deacetylases (HDACs) and are key events in the epigenetic regulation of gene expression. The application of HDAC inhibitors revealed a variety of T cell functions controlled by reversible lysine acetylation and HDAC1, HDAC2, HDAC3, HDAC7 and HDAC9 have been implicated in regulating T cell development and function. Nevertheless, unique functions of individual HDAC members in T cells and specific T cell functions that are regulated by HDACs are still only poorly understood. We previously showed that T cell-specific loss of HDAC1 (using the Cd4Cre deleter strain) leads to enhanced allergic airway inflammation and increased Th2 cytokine production. Interestingly, late T cell development was not impaired in these mice. However, HDAC2 was up-regulated in the absence of HDAC1, thus we hypothesized compensatory pathways/function between these two closely related class I HDAC family members in T cells. To investigate redundant and non-redundant functions of HDAC1 and HDAC2, we generated mice with a conditional T cell-specific (using Cd4Cre) combined loss of HDAC1 and HDAC2. As part of our study, we determined and compared the transcriptome of peripheral wild-type and HDAC1/2-null CD4+ T cells. Since loss of HDAC1/HDAC2 during late T cell development led to the appearance of MHC class II-selected CD4+ helper T cells that expressed CD8 lineage genes such as Cd8a and Cd8b1, we also analyzed the transcriptome of HDAC1/2-null CD4+CD8+ T cells.
2014-03-30 | E-MTAB-2184 | biostudies-arrayexpress
Project description:Histone deacetylases (Hdac) remove acetyl groups from proteins, influencing global and specific gene expression. Hdacs control inflammation, as shown by Hdac inhibitor-dependent protection from DSS-induced murine colitis. While tissue-specific Hdac knockouts show redundant and specific functions, little is known of their intestinal epithelial cell (IEC) role. We have shown previously that dual Hdac1/Hdac2 IEC-specific loss disrupts cell proliferation and determination, with decreased secretory cell numbers and altered barrier function. We thus investigated how compound Hdac1/Hdac2 or Hdac2 IEC-specific deficiency alters the inflammatory response. Floxed Hdac1 and Hdac2 and villin-Cre mice were interbred. Compound Hdac1/Hdac2 IEC-deficient mice showed chronic basal inflammation, with increased basal Disease Activity Index (DAI) and deregulated Reg gene colonic expression. DSS-treated dual Hdac1/Hdac2 IEC-deficient mice displayed increased DAI, histological score, intestinal permeability and inflammatory gene expression. In contrast to double knockouts, Hdac2 IEC-specific loss did not affect IEC determination and growth, nor result in chronic inflammation. However, Hdac2 disruption protected against DSS colitis, as shown by decreased DAI, intestinal permeability and caspase-3 cleavage. Hdac2 IEC-specific deficient mice displayed increased expression of IEC gene subsets, such as colonic antimicrobial Reg3b and Reg3g mRNAs, and decreased expression of immune cell function-related genes. Our data show that Hdac1 and Hdac2 are essential IEC homeostasis regulators. IEC-specific Hdac1 and Hdac2 may act as epigenetic sensors and transmitters of environmental cues and regulate IEC-mediated mucosal homeostatic and inflammatory responses. Different levels of IEC Hdac activity may lead to positive or negative outcomes on intestinal homeostasis during inflammation Total RNAs from the colon of three control and three Hdac2 IEC-specific knockout mice were isolated with the Rneasy kit (Qiagen, Mississauga, ON, Canada).
2014-02-08 | E-GEOD-54785 | biostudies-arrayexpress
Project description:Preliminary manuscript abstract: Class I histone deacetylases HDAC1 and HDAC2 contribute to cell proliferation and are commonly upregulated in urothelial carcinoma (UC). To evaluate whether specific inhibition of HDAC1 and HDAC2 might serve as an appropriate therapy of UC we applied specific pharmacological inhibition of HDAC1 and HDAC2 with the two selective class I HDAC inhibitors Romidepsin and Givinostat. Treatment with the pan HDAC inhibitor SAHA served as an additional control. Romidepsin and Givinostat significantly reduced proliferation and clonogenicity of UC cells with minor effects on non-tumorigenic cells. Furthermore, compounds induced primarily S-phase disturbances and non-apoptotic cell death. Results of microarray analysis of HDAC inhibitor treated cells match with observed phenotype after pharmacological HDAC1 and HDAC2 inhibition in UC cells.
2016-01-31 | GSE70120 | GEO