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HDAC1 HDAC2

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https://www.readbyqxmd.com/read/29765516/selective-dissociation-between-lsd1-and-gfi1b-by-a-lsd1-inhibitor-ncd38-induces-the-activation-of-erg-super-enhancer-in-erythroleukemia-cells
#1
Ryusuke Yamamoto, Masahiro Kawahara, Shinji Ito, Junko Satoh, Goichi Tatsumi, Masakatsu Hishizawa, Takayoshi Suzuki, Akira Andoh
Lysine-specific demethylase 1 (LSD1) is a histone modifier for transcriptional repression involved in the regulation of hematopoiesis. We previously reported that a LSD1 inhibitor NCD38 induces transdifferentiation from erythroid lineage to granulomonocytic lineage and exerts anti-leukemia effect through de-repression of the specific super-enhancers of hematopoietic regulators including ERG in a human erythroleukemia cell line, HEL. However, the mechanistic basis for this specificity of NCD38 has remained unclear...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29734115/transcriptional-and-posttranscriptional-repression-of-histone-deacetylases-by-docosahexaenoic-acid-in-macrophages
#2
Tho X Pham, Minkyung Bae, Yoojin Lee, Young-Ki Park, Ji-Young Lee
Histone deacetylation is one of the posttranslational modifications of histones by which eukaryotic cells alter gene transcription. Although fatty acids are the best known macronutrients that modulate gene expression in inflammatory pathways, it is unclear whether common fatty acids in diets can regulate the expression of histone deacetylases (HDACs) in macrophages. We determined the effects of fatty acids, including palmitic acid (PA), oleic acid (OA), linoleic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the expression of HDAC isoforms in RAW 264...
March 10, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29731773/romidepsin-promotes-osteogenic-and-adipocytic-differentiation-of-human-mesenchymal-stem-cells-through-inhibition-of-histondeacetylase-activity
#3
Dalia Ali, Elna P Chalisserry, Muthurangan Manikandan, Rimi Hamam, Musaad Alfayez, Moustapha Kassem, Abdullah Aldahmash, Nehad M Alajez
Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM) exhibited enhanced adipocytic and osteoblastic differentiation...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29712641/histone-deacetylases-1-and-2-regulate-the-transcriptional-programs-of-nephron-progenitors-and-renal-vesicles
#4
Hongbing Liu, Shaowei Chen, Xiao Yao, Yuwen Li, Chao-Hui Chen, Jiao Liu, Zubaida Saifudeen, Samir S El-Dahr
Nephron progenitor cells (NPC) are Six2-positive metanephric mesenchyme cells, which undergo self-renewal and differentiation to give rise to nephrons until the end of nephrogenesis. HDACs are a group of epigenetic regulators that control cell fate but their role in balancing NPC renewal and differentiation is unknown. Here, we report that NPC-specific deletion of HDAC1 and HDAC2 genes in mice results in early postnatal lethality due to renal hypo-dysplasia and loss of NPC. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer...
April 30, 2018: Development
https://www.readbyqxmd.com/read/29613828/activation-of-class-i-histone-deacetylases-contributes-to-mitochondrial-dysfunction-in-cardiomyocytes-with-altered-complex-activities
#5
Baigalmaa Lkhagva, Yu-Hsun Kao, Ting-I Lee, Ting-Wei Lee, Wan-Li Cheng, Yi-Jen Chen
Histone deacetylases (HDACs) play vital roles in the pathophysiology of heart failure, which is associated with mitochondrial dysfunction. Tumor necrosis factor-α (TNF-α) contributes to the genesis of heart failure and impairs mitochondria. This study evaluated the role of HDACs in TNF-α-induced mitochondrial dysfunction and investigated their therapeutic potential and underlying mechanisms. We measured mitochondrial oxygen consumption rate (OCR) and ATP production using Seahorse XF24 extracellular flux analyzer and bioluminescent assay in control and TNF-α (10 ng/ml, 24 h)-treated HL-1 cells with or without HDAC inhibition...
April 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29590644/acetylation-of-gata4-on-lysine-residue-k313-promotes-osteoblastic-cells-growth
#6
Wenjun You, Lijuan Song, Kun Wang
BACKGROUND/AIMS: GATA4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects. Here, we aimed to explore the functional impacts of GATA4 acetylation on osteoporosis (OS). METHODS: GATA4 acetylation in hFOB1.19 and 293T cells was detected after exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted to determine which HATs and HDACs was involved in the modulation of GATA4 acetylation/deacetylation, and to identify the acetylation site...
March 22, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29587244/epigenetic-regulation-of-vascular-nadph-oxidase-expression-and-reactive-oxygen-species-production-by-histone-deacetylase-dependent-mechanisms-in-experimental-diabetes
#7
Simona-Adriana Manea, Mihaela-Loredana Antonescu, Ioana Madalina Fenyo, Monica Raicu, Maya Simionescu, Adrian Manea
Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox) contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC)-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29579541/set-promotes-h2ak9-acetylation-by-suppressing-hdac1-in-trichloroethylene-induced-hepatic-cytotoxicity
#8
Weixue Lu, Zhihong Chen, Xiaohu Ren, Wei Liu, Rongxia Deng, Jianhui Yuan, Xinfeng Huang, Weiguo Zhu, Jianjun Liu
Trichloroethylene (TCE) was widely used as an industrial solvent which could cause severe liver damage. The histone chaperone SET have been identified as an important mediator of TCE-induced hepatic cytotoxicity in our previous study; however, the underlying regulatory mechanisms remain poorly understood. In this study, we found a total of 136 histone acetylation sites involved in TCE-induced hepatic cytotoxicity with the technique of Triton-acid-urea polyacrylamide gel electrophoresis (TAU-PAGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
March 17, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29562197/a-developmental-switch-in-microglial-hdac-function
#9
Hansruedi Mathys, Jay Penney, Li-Huei Tsai
The epigenetic mechanisms controlling microglia functions are largely unknown. In this issue of Immunity, Datta et al. (2018) uncover surprising and distinct effects of deleting the epigenetic regulators HDAC1 and HDAC2 during microglial development versus during the course of neurodegeneration.
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29548672/histone-deacetylases-1-and-2-regulate-microglia-function-during-development-homeostasis-and-neurodegeneration-in-a-context-dependent-manner
#10
Moumita Datta, Ori Staszewski, Elena Raschi, Maximilian Frosch, Nora Hagemeyer, Tuan Leng Tay, Thomas Blank, Mario Kreutzfeldt, Doron Merkler, Stephanie Ziegler-Waldkirch, Patrick Matthias, Melanie Meyer-Luehmann, Marco Prinz
Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, Hdac1 and Hdac2. Prenatal ablation of Hdac1 and Hdac2 impaired microglial development. Mechanistically, the promoters of pro-apoptotic and cell cycle genes were hyperacetylated in absence of Hdac1 and Hdac2, leading to increased apoptosis and reduced survival...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29511350/tbx3-promotes-proliferation-of-papillary-thyroid-carcinoma-cells-through-facilitating-prc2-mediated-p57-kip2-repression
#11
Xiaomeng Li, Xianhui Ruan, Peitao Zhang, Yang Yu, Ming Gao, Shukai Yuan, Zewei Zhao, Jie Yang, Li Zhao
The T-box transcription factor TBX3 has been implicated in the patterning and differentiation of a number of tissues during embryonic development, and is overexpressed in a variety of cancers; however, the precise function of TBX3 in papillary thyroid carcinoma (PTC) development remains to be determined. In the current study, we report downregulation of TBX3 in PTC cells delays the G1/S-phase transition, decreases cell growth in vitro, and inhibits tumor formation in vivo. We identified p57KIP2 as a novel downstream target that serves as the key mediator of TBX3's control over PTC cell proliferation...
March 7, 2018: Oncogene
https://www.readbyqxmd.com/read/29494986/low-expression-of-gfi-1-gene-is-associated-with-panobinostat-resistance-in-acute-myeloid-leukemia-through-influencing-the-level-of-ho-1
#12
Bingqing Cheng, Sishi Tang, Nana Zhe, Dan Ma, Kunlin Yu, Danna Wei, Zheng Zhou, Tingting Lu, Jishi Wang, Qin Fang
To improve the treatment outcomes of acute myeloid leukemia (AML), epigenetic modification has been widely tested and used in recent years. However, drug-resistance is still a choke point to cure the malignancy. The growth factor independent 1 transcriptional repressor (GFI-1), as a zinc-finger transcriptional repressor, can bind histone deacetylases to allow the transcriptional repression. According to the finding of our study, AML patients with low level of GFI-1 not only implicated poor prognosis but also caused Panobinostat-resistance...
April 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29484736/pharmacological-or-transcriptional-inhibition-of-both-hdac1-and-2-leads-to-cell-cycle-blockage-and-apoptosis-via-p21-waf1-cip1-and-p19-ink4d-upregulation-in-hepatocellular-carcinoma
#13
Hengyu Zhou, Ying Cai, Dina Liu, Menghui Li, Yu Sha, Wenlu Zhang, Kai Wang, Jianping Gong, Ni Tang, Ailong Huang, Jie Xia
OBJECTIVES: Histone deacetylases (HDACs) are commonly dysregulated in cancer and represent promising therapeutic targets. However, global HDAC inhibitors have shown limited efficacy in the treatment of solid tumours, including hepatocellular carcinoma (HCC). In this study, we investigated the therapeutic effect of selectively inhibiting HDAC1 and 2 in HCC. METHODS: HDAC1 inhibitor Tacedinaline (CI994), HDAC2 inhibitor Santacruzamate A (CAY10683), HDAC1/2 common inhibitor Romidepsin (FK228) and global HDAC inhibitor Vorinostat (SAHA) were used to treat HCC cells...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29482060/inhibition-of-class-iia-histone-deacetylase-activity-by-gallic-acid-sulforaphane-tmp269-and-panobinostat
#14
Sin Young Choi, Hae Jin Kee, Li Jin, Yuhee Ryu, Simei Sun, Gwi Ran Kim, Myung Ho Jeong
Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9)...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29481474/clinicopathological-features-and-prediction-values-of-hdac1-hdac2-hdac3-and-hdac11-in-classical-hodgkin-lymphoma
#15
Renhong Huang, Xiaowei Zhang, Sadia Sophia, Zhijun Min, Xiaojian Liu
Histone deacetylases (HDACs) are involved in multiple physical and pathological processes in classical Hodgkin lymphoma (cHL). The prognostic value of HDACs in cHL patients has not been discussed. The aim of the current study is to investigate the HDAC1, HDAC2, HDAC3, and HDAC11 expressions, and to evaluate the correlation of HDAC1, HDAC2, HDAC3, and HDAC11 expressions with the survival rate in cHL patients. We retrospectively analyzed clinicopathological data of 28 patients who were diagnosed with cHL between August 2002 and March 2010...
April 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29472538/hdac1-and-hdac2-integrate-checkpoint-kinase-phosphorylation-and-cell-fate-through-the-phosphatase-2a-subunit-pr130
#16
Anja Göder, Claudia Emmerich, Teodora Nikolova, Nicole Kiweler, Maria Schreiber, Toni Kühl, Diana Imhof, Markus Christmann, Thorsten Heinzel, Günter Schneider, Oliver H Krämer
Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show that the histone deacetylases HDAC1/HDAC2 sustain the phosphorylation of the checkpoint kinases ATM, CHK1 and CHK2, activity of the cell cycle gatekeeper kinases WEE1 and CDK1, and induction of the tumour suppressor p53 in response to stalled DNA replication. Consequently, HDAC inhibition upon replicative stress promotes mitotic catastrophe. Mechanistically, HDAC1 and HDAC2 suppress the expression of PPP2R3A/PR130, a regulatory subunit of the trimeric serine/threonine phosphatase 2 (PP2A)...
February 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29464997/the-discovery-of-novel-hdac3-inhibitors-via-virtual-screening-and-in-vitro-bioassay
#17
Jie Xia, Huabin Hu, Wenjie Xue, Xiang Simon Wang, Song Wu
Histone deacetylase 3 (HDAC3) is a potential target for the treatment of human diseases such as cancers, diabetes, chronic inflammation and neurodegenerative diseases. Previously, we proposed a virtual screening (VS) pipeline named "Hypo1_FRED_SAHA-3" for the discovery of HDAC3 inhibitors (HDAC3Is) and had thoroughly validated it by theoretical calculations. In this study, we attempted to explore its practical utility in a large-scale VS campaign. To this end, we used the VS pipeline to hierarchically screen the Specs chemical library...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29453984/gata3-acetylation-at-k119-by-cbp-inhibits-cell-migration-and-invasion-in-lung-adenocarcinoma
#18
Xueying Li, Jiaqi Jin, Siyuan Yang, Weizhi Xu, Xianbin Meng, Haiteng Deng, Jun Zhan, Shan Gao, Hongquan Zhang
GATA3 is a transcriptional factor involved in the development of multiple organs. Post translational modifications of GATA3 are critical to its function. Here, we report that GATA3 interacts with and is acetylated by the acetyltransferase CBP. Class I deacetylases HDAC1, HDAC2 and HDAC3 deacetylate GATA3. The major acetylated site of GATA3 in lung adenocarcinoma cells was determined at lysine 119 (AcK119). Functionally, GATA3-acetylation mimics K119Q mutant was found to inhibit lung adenocarcinoma cell migration and invasion with concomitant downregulation of EMT-controlling transcriptional factors Slug, Zeb1 and Zeb2...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29449904/expression-profiling-of-chromatin-modifying-enzymes-and-global-dna-methylation-in-cd4-t-cells-from-patients-with-chronic-hiv-infection-at-different-hiv-control-and-progression-states
#19
Roberta Nicoleta Bogoi, Alicia de Pablo, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Helem Haydee Vilchez-Rueda, Victor Asensi, Rosa Rodriguez, Victor Toledano, Berta Rodés
Background: Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome causes global disruption of the chromatin environment. The abundance level of various chromatin-modifying enzymes produces these alterations and affects both the provirus and cellular gene expression. Here, we investigated potential changes in enzyme expression and global DNA methylation in chronically infected individuals with HIV-1 and compared these changes with non-HIV infected individuals...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29448109/hdac1-regulates-the-stability-of-glutamate-carboxypeptidase-ii-protein-by-modulating-acetylation-status-of-lysine-479-residue
#20
Ji-Young Choi, Jun-Hyeok Ko, Sangmee Ahn Jo
Our previous study showed that the level of glutamate carboxypeptidase II (GCPII) protein is regulated by valproic acid, a histone deacetylase (HDAC) inhibitor, through acetylation of lysine residue in the GCPII protein in human astrocytes, U-87MG. The present study further investigated which HDAC subtype is involved in the acetylation of GCPII. The results revealed that GCPII interacted with HDAC1 but not with HDAC2, HDAC3, HDAC4, HDAC5, and HDAC6. Overexpression of catalytic domain (1-56 aa)-deleted HDAC1, which poorly binds to GCPII, enhanced lysine acetylation in GCPII and increased the level of GCPII protein when compared with that of the wild-type HDAC1...
February 26, 2018: Biochemical and Biophysical Research Communications
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