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https://www.readbyqxmd.com/read/29301935/-inhibition-of-histone-h3k27-demethylase-selectively-modulates-inflammatory-phenotypes-of-natural-killer-cells
#1
Adam Cribbs, Edward S Hookway, Graham Wells, Morten Lindow, Susanna Obad, Henrik Oerum, Rab K Prinjha, Nick Athanasou, Aneka Sowman, Martin Philpott, Henry Penn, Kalle Soderstrom, Marc Feldmann, Udo Oppermann
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically, but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29247011/histone-demethylase-activity-of-utx-is-essential-for-viability-and-regulation-of%C3%A2-hox-gene-expression-in%C3%A2-drosophila
#2
Ömer Copur, Jürg Müller
The trimethylation of histone H3 at lysine 27 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2) is essential for repression of Polycomb target genes. The role of enzymatic demethylation of H3K27me3 by the KDM6-family demethylases Utx, Uty and JmjD3 is however less clear. Studies in both mice and worms led to the proposal that KDM6 proteins but not their H3K27me3 demethylase activity is critical for normal development. Here, we investigated the requirement of the demethylase activity of the single KDM6 family member Utx in Drosophila We generated Drosophila expressing full-length but catalytic inactive Utx protein and found that these mutants show the same phenotypes like animals lacking Utx protein...
December 15, 2017: Genetics
https://www.readbyqxmd.com/read/29245970/calcitriol-induces-cell-senescence-of-kidney-cancer-through-jmjd3-mediated-histone-demethylation
#3
Yongqing Shen, Dan Yu, Pan Qi, Xuliang Wang, Xiaoqiang Guo, Aili Zhang
Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O (P<0.05). Calcitriol also induced cell apoptosis and senescence of 786-O and ACHN (P<0...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227285/shifts-in-podocyte-histone-h3k27me3-regulate-mouse-and-human-glomerular-disease
#4
Syamantak Majumder, Karina Thieme, Sri N Batchu, Tamadher A Alghamdi, Bridgit B Bowskill, M Golam Kabir, Youan Liu, Suzanne L Advani, Kathryn E White, Laurette Geldenhuys, Karthik K Tennankore, Penelope Poyah, Ferhan S Siddiqi, Andrew Advani
Histone protein modifications control fate determination during normal development and dedifferentiation during disease. Here, we set out to determine the extent to which dynamic changes to histones affect the differentiated phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we examined the consequences of shifting the balance of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29224413/low-hox-gene-expression-in-pml-rar%C3%AE-positive-leukemia-results-from-suppressed-histone-demethylation
#5
Kateřina Rejlová, Alena Musilová, Karolina Škvárová Kramarzová, Markéta Žaliová, Karel Fišer, Meritxell Alberich-Jorda, Jan Trka, Júlia Starková
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene has distinct HOX gene signature in comparison to other subtypes of AML patients although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients...
December 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29161520/ezh2-histone-methyltransferase-and-jmjd3-histone-demethylase-implications-in-prostate-cancer
#6
Mouhamed Idrissou, Marine Daures, Amani Ben Jemia, Gaëlle Judes, Khaldoun Rifaï, Frédérique Penault-Llorca, Yves-Jean Bignon, Laurent Guy, Dominique Bernard-Gallon
No abstract text is available yet for this article.
November 21, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29074105/endogenous-hydrogen-sulfide-regulates-histone-demethylase-jmjd3-mediated-inflammatory-response-in-lps-stimulated-macrophages-and-in-a-mouse-model-of-lps-induced-septic-shock
#7
Siyu Liu, Xiling Wang, Lilong Pan, Weijun Wu, Di Yang, Ming Qin, Wanwan Jia, Chenxi Xiao, Fen Long, Junbo Ge, Xinhua Liu, YiZhun Zhu
Overproduction of inflammatory mediators contributes to uncontrolled inflammation during endotoxin shock.Cystathionine-γ-lyase (CSE), an enzyme involved in hydrogen sulfide (H2S) biosynthesis, has potential anti-inflammatory activity in a variety of inflammatory diseases. Jumonji domain-containing protein 3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in macrophage activation, but its function in CSE-mediated anti-inflammatory activities remains unknown. In the present study CSE was found to be upregulated in macrophages and mouse lipopolysaccharide (LPS) challenge models...
October 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29070530/the-histone-demethylase-jumonji-domain-containing-protein-3-jmjd3-regulates-fibroblast-activation-in-systemic-sclerosis
#8
Christina Bergmann, Amelie Brandt, Benita Merlevede, Ludwig Hallenberger, Clara Dees, Thomas Wohlfahrt, Sebastian Pötter, Yun Zhang, Chih-Wei Chen, Tatiana Mallano, Ruifang Liang, Rosebeth Kagwiria, Alexander Kreuter, Ioanna Pantelaki, Aline Bozec, David Abraham, Ralf Rieker, Andreas Ramming, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis...
October 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29036979/-role-of-ash2-absent-small-or-homeotic-like-and-jumonji-domain-containing-protein-3-on-histone-methylation-of-interferon-gamma-gene-and-their-associations-with-vascular-damage-of-kawasaki-disease
#9
J H Mei, G Tang, Q Wang, P Q Wen, M G Xu, D Cui, D L Ma, C Liu, G B Wang
Objective: To investigate the impacts of ash2 (absent, small, or homeotic)-like (Ash2L) and Jumonji domain-containing protein 3 (Jmjd3) on histone methylation of interferon-gamma(IFN-γ) gene and association with vascular damage of Kawasaki disease (KD) in acute phase. Methods: This study was performed among 36 children with KD in acute phase (KD group) and 28 age-matched health children (control group), who were treated or underwent physical examination in our hospital between February 2015 and June 2016. Patients were further divided into KD groups with or without coronary artery lesions (KD-CAL(+) , 16 cases; KD-CAL(-), 20 cases)...
September 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29022922/rankl-mediated-harmonious-dialogue-between-fetus-and-mother-guarantees-smooth-gestation-by-inducing-decidual-m2-macrophage-polarization
#10
Yu-Han Meng, Wen-Jie Zhou, Li-Ping Jin, Li-Bing Liu, Kai-Kai Chang, Jie Mei, Hui Li, Jian Wang, Da-Jin Li, Ming-Qing Li
Decidual macrophages (dMϕ) contribute to maternal-fetal tolerance. However, the mechanism of dMϕ differentiation during pregnancy is still largely unknown. Here, we report that receptor activator for nuclear factor-κ B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells (DSCs), polarizes dMϕ toward a M2 phenotype. This polarization is mediated through activation of Akt/signal transducer and activator of transcription 6 (STAT6) signaling, which is associated with the upregulation of histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMϕ...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978140/the-pharmacological-role-of-histone-demethylase-jmjd3-inhibitor-gsk-j4-on-glioma-cells
#11
Aixia Sui, Yongbing Xu, Yitong Li, Qilu Hu, Zeyang Wang, Hongtao Zhang, Junjie Yang, Xiaoqiang Guo, Wenqing Zhao
Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system, and lack of effective treatment. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. In the present study, histone H3K27 demethylase jumonji domain-containing protein 3 (JMJD3) was investigated as target for glioma treatment. The mRNA of JMJD3 was overexpressed in glioblastoma tissues compared to normal brain tissues (P<0.05). The content of JMJD3 was also higher in glioma cells than in human brain microvascular endothelial cell (hCMEC), and the corresponding level of H3K27me3 was decreased (P<0...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#12
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28952292/triptolide-promotes-senescence-of-prostate-cancer-cells-through-histone-methylation-and-heterochromatin-formation
#13
Ousman Tamgue, Ming Lei
Background: Triptolide is a medicinal herb-derived diterpene triepoxide with potent anti-tumor activity, mainly ,correlated with its ability to inhibit and inactivate subunits of RNA polymerase II, thereby suppressing global gene transcription. Epigenetic imbalance including histone methylation are well known to play important roles in prostate cancer (PCa) onset and progression. The goal of this study was to investigate whether triptolide might exert anti-PCa influence by reshaping the histone methylation landscape...
September 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28947543/h3k27-methylation-dynamics-during-cd4-t-cell-activation-regulation-of-jak-stat-and-il12rb2-expression-by-jmjd3
#14
Sarah A LaMere, Ryan C Thompson, Xiangzhi Meng, H Kiyomi Komori, Adam Mark, Daniel R Salomon
The changes to the epigenetic landscape in response to Ag during CD4 T cell activation have not been well characterized. Although CD4 T cell subsets have been mapped globally for numerous epigenetic marks, little has been done to study their dynamics early after activation. We have studied changes to promoter H3K27me3 during activation of human naive and memory CD4 T cells. Our results show that these changes occur relatively early (1 d) after activation of naive and memory cells and that demethylation is the predominant change to H3K27me3 at this time point, reinforcing high expression of target genes...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28894299/dhea-inhibits-acute-microglia-mediated-inflammation-through-activation-of-the-trka-akt1-2-creb-jmjd3-pathway
#15
V I Alexaki, G Fodelianaki, A Neuwirth, C Mund, A Kourgiantaki, E Ieronimaki, K Lyroni, M Troullinaki, C Fujii, W Kanczkowski, A Ziogas, M Peitzsch, S Grossklaus, B Sönnichsen, A Gravanis, S R Bornstein, I Charalampopoulos, C Tsatsanis, T Chavakis
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28890349/molecular-hydrogen-modulates-gene-expression-via-histone-modification-and-induces-the-mitochondrial-unfolded-protein-response
#16
Sayaka Sobue, Chisato Inoue, Fumiko Hori, Shanlou Qiao, Takashi Murate, Masatoshi Ichihara
Molecular hydrogen (H2) is a biologically active gas that is used medically to ameliorate various systemic pathological conditions. H2 also regulates gene expression involved in intracellular signaling and metabolic pathways. However, it is unclear whether H2 affects gene expression directly or through indirect effects as a consequence of health improvement. Therefore, we attempted to identify genes that exhibit similar changes in expression in response to H2 by employing DNA microarrays and gene set enrichment analysis to analyze RNA from liver and lung of rats and mice with or without dietary stress...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#17
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
January 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/28747667/rna-sequencing-reveals-resistance-of-tlr4-ligand-activated-microglial-cells-to-inflammation-mediated-by-the-selective-jumonji-h3k27-demethylase-inhibitor
#18
Amitabh Das, Sarder Arifuzzaman, Taeho Yoon, Sun Hwa Kim, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747631/jmjd3-and-nf-%C3%AE%C2%BAb-dependent-activation-of-notch1-gene-is-required-for-keratinocyte-migration-during-skin-wound-healing
#19
Jungtae Na, Jee Yoon Shin, Hayan Jeong, Jee Youn Lee, Beom Joon Kim, Won Sun Kim, Tae Young Yune, Bong-Gun Ju
It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-κB in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-κB in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743103/lanthanum-chloride-inhibits-lps-mediated-expressions-of-pro-inflammatory-cytokines-and-adhesion-molecules-in-huvecs-involvement-of-nf-%C3%AE%C2%BAb-jmjd3-signaling
#20
Xia Chen, Min Xiu, Juanjuan Xing, Shaoqing Yu, Dinghong Min, Fei Guo
BACKGROUND/AIMS: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs). METHODS: Primary cultured HUVECs were pretreated with 2.5 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence...
2017: Cellular Physiology and Biochemistry
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