Similar Datasets
Project description:We report the chromatin accessibility with knock down of HDAC1 and HDAC2 from the epithelium of the adult mouse kidney
2021-12-27 | GSE181557 | GEO
Project description:Histone deacetylase (HDAC) enzymes regulate transcription through epigenetic modification of chromatin structure, but their specific functions in the kidney remain elusive. We discovered that the human kidney expresses class I HDACs. Kidney medulla-specific inhibition of class I HDACs in the rat during high-salt feeding results in hypertension, polyuria, hypokalemia, and nitric oxide deficiency. Three new inducible murine models were used to determine that HDAC1 and HDAC2 in the kidney epithelium are necessary for maintaining epithelial integrity and maintaining fluid-electrolyte balance during increased dietary sodium intake. Moreover, single-nucleus RNA-sequencing determined that epithelial HDAC1 and HDAC2 are necessary for expression of many sodium or water transporters and channels. In performing a systematic review and meta-analysis of serious adverse events associated with clinical HDAC inhibitor use, we found that HDAC inhibitors increased the odds ratio of experiencing fluid-electrolyte disorders, such as hypokalemia. This study provides insight on the mechanisms of potential serious adverse events with HDAC inhibitors, which may be fatal to critically ill patients. In conclusion, kidney tubular HDACs provide a link between the environment, such as consumption of high-salt diets, and regulation of homeostatic mechanisms to remain in fluid-electrolyte balance.
| S-EPMC7455138 | biostudies-literature
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:Fluid-electrolyte homeostasis requires histone deacetylase function
| PRJNA624046 | ENA
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:DC progenitors adapt their transcriptional program during development generating different subsets. How chromatin modifications modulate these processes is unclear. Here we investigate the impact of histone deacetylation on DCs by genetically deleting HDAC1 or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 isn’t critical for DC development, HDAC1 deletion impairs pro- and mature pDC generation and affects ESAM+cDC2 differentiation from tDC and pre-cDC2, whereas cDC1s are unchanged. HDAC1 knock-down in human hematopoietic cells also impairs cDC2 development highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility and histone-acetylation of the transcription factors IRF4, IRF8 and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically enhancing tumor surveillance through increased cDC1 maturation and IL-12 production driving Th1-mediated immunity and CD8+T-cell recruitment. Our study reveals the importance of histone-acetylation in DC development and anti-tumor immunity suggesting DC-targeted therapeutic strategies for immuno-oncology.
2024-05-30 | GSE266583 | GEO
Project description:DC progenitors adapt their transcriptional program during development generating different subsets. How chromatin modifications modulate these processes is unclear. Here we investigate the impact of histone deacetylation on DCs by genetically deleting HDAC1 or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 isn’t critical for DC development, HDAC1 deletion impairs pro- and mature pDC generation and affects ESAM+cDC2 differentiation from tDC and pre-cDC2, whereas cDC1s are unchanged. HDAC1 knock-down in human hematopoietic cells also impairs cDC2 development highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility and histone-acetylation of the transcription factors IRF4, IRF8 and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically enhancing tumor surveillance through increased cDC1 maturation and IL-12 production driving Th1-mediated immunity and CD8+T-cell recruitment. Our study reveals the importance of histone-acetylation in DC development and anti-tumor immunity suggesting DC-targeted therapeutic strategies for immuno-oncology.
2024-05-30 | GSE266582 | GEO
Project description:DC progenitors adapt their transcriptional program during development generating different subsets. How chromatin modifications modulate these processes is unclear. Here we investigate the impact of histone deacetylation on DCs by genetically deleting HDAC1 or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 isn’t critical for DC development, HDAC1 deletion impairs pro- and mature pDC generation and affects ESAM+cDC2 differentiation from tDC and pre-cDC2, whereas cDC1s are unchanged. HDAC1 knock-down in human hematopoietic cells also impairs cDC2 development highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility and histone-acetylation of the transcription factors IRF4, IRF8 and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically enhancing tumor surveillance through increased cDC1 maturation and IL-12 production driving Th1-mediated immunity and CD8+T-cell recruitment. Our study reveals the importance of histone-acetylation in DC development and anti-tumor immunity suggesting DC-targeted therapeutic strategies for immuno-oncology.
2024-05-30 | GSE266581 | GEO
Project description:Hdac1 and 2 are important regulators of developmental processes. In this study we created microglia specific compound Hdac1 and Hdac2 knock out mice. Pre-natal ablation of both Hdac1 and 2 from microglia leads to reduced cell number and altered cell morphology. To investigate how Hdac1 and 2 knock out in microglia alters cellular gene expression profile we carried out RNA-seq analysis at different time points.
2018-03-14 | GSE98822 | GEO
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