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https://www.readbyqxmd.com/read/27857213/the-modification-of-tet1-in-male-germline-stem-cells-and-interact-with-pcna-hdac1-to-promote-their-self-renewal-and-proliferation
#1
Liming Zheng, Yuanxin Zhai, Na Li, Fanglin Ma, Haijing Zhu, Xiaomin Du, Guangpeng Li, Jinlian Hua
Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27802135/transient-ectopic-expression-of-the-histone-demethylase-jmjd3-accelerates-the-differentiation-of-human-pluripotent-stem-cells
#2
Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B H Ko, Minoru S H Ko
Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c)...
October 15, 2016: Development
https://www.readbyqxmd.com/read/27800026/hypoxia-increases-genome-wide-bivalent-epigenetic-marking-by-specific-gain-of-h3k27me3
#3
Peggy Prickaerts, Michiel E Adriaens, Twan van den Beucken, Elizabeth Koch, Ludwig Dubois, Vivian E H Dahlmans, Caroline Gits, Chris T A Evelo, Michelle Chan-Seng-Yue, Bradly G Wouters, Jan Willem Voncken
BACKGROUND: Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27779233/microrna-939-restricts-hepatitis-b-virus-by-targeting-jmjd3-mediated-and-c-ebp%C3%AE-coordinated-chromatin-remodeling
#4
Cuncun Chen, Min Wu, Wen Zhang, Wei Lu, Min Zhang, Zhanqing Zhang, Xiaonan Zhang, Zhenghong Yuan
Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27755585/microrna-941-expression-in-polymorphonuclear-granulocytes-is-not-related-to-granulomatosis-with-polyangiitis
#5
Jesper Brink Svendsen, Bo Baslund, Elisabeth Præstekjær Cramer, Nicolas Rapin, Niels Borregaard, Jack Bernard Cowland
Jumonji Domain-Containing Protein 3 (JMJD3)/lysine demethylase 6B (KDM6B) is an epigenetic modulator that removes repressive histone marks on genes. Expression of KDM6B mRNA is elevated in leukocytes from patients with ANCA-associated vasculitis (AAV) and has been suggested to be the reason for higher proteinase 3 (PR3) mRNA expression in these cells due to derepression of PRTN3 gene transcription. MicroRNA-941 (miR-941) has been shown to target KDM6B mRNA and inhibit JMJD3 production. We therefore investigated whether polymorphonuclear granulocytes (PMNs) from patients suffering from granulomatosis with polyangiitis (GPA) have lower expression of miR-941 than healthy control donors as a biological cause for higher JMJD3 levels...
2016: PloS One
https://www.readbyqxmd.com/read/27737800/hypoxic-inhibition-of-jmjd3-reduces-h3k27me3-demethylation-and-induction-of-the-stat6-target-gene-ccl18
#6
Nathalie Dehne, Bernhard Brüne
Hypoxia, by activating transcription factors induces transcription of some genes but it also reduces mRNA synthesis by mechanisms that are poorly defined. Activation of human macrophages with interleukin (IL)-4 showed that up-regulation of some IL-4 target genes was reduced when macrophages were incubated at 1% oxygen. Hypoxia impaired induction of chemokine (C-C motif) ligand 18 (CCL18), although IL-4-induced DNA binding of the transcription factor STAT6 remained intact. In contrast, induction of serine peptidase inhibitor, Kunitz type (SPINT)2, another IL-4/STAT6 target gene, was not affected by hypoxia...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27651311/aberrant-jmjd3-expression-upregulates-slug-to-promote-migration-invasion-and-stem-cell-like-behaviors-in-hepatocellular-carcinoma
#7
Bo Tang, Guangying Qi, Fang Tang, Shengguang Yuan, Zhenran Wang, Xingsi Liang, Bo Li, Shuiping Yu, Jie Liu, Qi Huang, Yangchao Wei, Run Zhai, Biao Lei, Hongping Yu, Stephen Tomlinson, Songqing He
The Jumonji domain-containing chromatin remodeling factor JMJD3 has important roles in development and cancer. Here we report a pivotal role for JMJD3 in sustaining the phenotype of aggressive hepatocarcinomas (HCC). Expression levels of JMJD3 in clinical specimens of HCC correlated inversely with patient survival. In HCC cells, we found that enforcing its overexpression induced epithelial-mesenchymal transition (EMT), invasive migration, stem cell-like traits and metastatic properties. Conversely, silencing JMJD3 in HCC cells overexpressing it inhibited these aggressive phenotypes...
September 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27600842/the-tbr2-molecular-network-controls-cortical-neuronal-differentiation-through-complementary-genetic-and-epigenetic-pathways
#8
Alessandro Sessa, Ernesto Ciabatti, Daniela Drechsel, Luca Massimino, Gaia Colasante, Serena Giannelli, Takashi Satoh, Shizuo Akira, Francois Guillemot, Broccoli Vania
The T-box containing Tbr2 gene encodes for a transcription factor essential for the specification of the intermediate neural progenitors (INPs) originating the excitatory neurons of the cerebral cortex. However, its overall mechanism of action, direct target genes and cofactors remain unknown. Herein, we carried out global gene expression profiling combined with genome-wide binding site identification to determine the molecular pathways regulated by TBR2 in INPs. This analysis led to the identification of novel protein-protein interactions that control multiple features of INPs including cell-type identity, morphology, proliferation and migration dynamics...
September 6, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27532872/musashi-mediated-expression-of-jmjd3-a-h3k27me3-demethylase-is-involved-in-foamy-macrophage-generation-during-mycobacterial-infection
#9
Sahana Holla, Praveen Prakhar, Vikas Singh, Anupama Karnam, Tanushree Mukherjee, Kasturi Mahadik, Pankti Parikh, Amit Singh, R S Rajmani, Subbaraya G Ramachandra, Kithiganahalli Narayanaswamy Balaji
Foamy macrophages (FM)s harbor lipid bodies that not only assist mycobacterial persistence within the granulomas but also are sites for intracellular signaling and inflammatory mediators which are essential for mycobacterial pathogenesis. However, molecular mechanisms that regulate intracellular lipid accumulation in FMs during mycobacterial infection are not clear. Here, we report for the first time that jumonji domain containing protein (JMJD)3, a demethylase of the repressive H3K27me3 mark, orchestrates the expression of M...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27528513/the-histone-demethylase-inhibitor-gsk-j4-limits-inflammation-through-the-induction-of-a-tolerogenic-phenotype-on-dcs
#10
Cristian Doñas, Macarena Carrasco, Macarena Fritz, Carolina Prado, Gabriela Tejón, Francisco Osorio-Barrios, Valeria Manríquez, Paz Reyes, Rodrigo Pacheco, María Rosa Bono, Alejandra Loyola, Mario Rosemblatt
As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize that inhibition of JMJD3 may attenuate autoimmune disorders. We found that in vivo administration of GSK-J4, a selective inhibitor of JMJD3 and UTX, ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). In vitro experiments revealed that the anti-inflammatory effect of GSK-J4 was exerted through an effect on dendritic cells (DCs), promoting a tolerogenic profile characterized by reduced expression of costimulatory molecules CD80/CD86, an increased expression of tolerogenic molecules CD103 and TGF-β1, and reduced secretion of proinflammatory cytokines IL-6, IFN-γ, and TNF...
August 12, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27525438/granulocyte-macrophage-colony-stimulating-factor-induces-ccl17-production-via-irf4-to-mediate-inflammation
#11
Adrian Achuthan, Andrew D Cook, Ming-Chin Lee, Reem Saleh, Hsu-Wei Khiew, Melody W N Chang, Cynthia Louis, Andrew J Fleetwood, Derek C Lacey, Anne D Christensen, Ashlee T Frye, Pui Yeng Lam, Hitoshi Kusano, Koji Nomura, Nancy Steiner, Irmgard Förster, Stephen L Nutt, Moshe Olshansky, Stephen J Turner, John A Hamilton
Data from preclinical and clinical studies have demonstrated that granulocyte macrophage colony-stimulating factor (GM-CSF) can function as a key proinflammatory cytokine. However, therapies that directly target GM-CSF function could lead to undesirable side effects, creating a need to delineate downstream pathways and mediators. In this work, we provide evidence that GM-CSF drives CCL17 production by acting through an IFN regulatory factor 4-dependent (IRF4-dependent) pathway in human monocytes, murine macrophages, and mice in vivo...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27458035/the-roles-of-histone-demethylase-utx-and-jmjd3-kdm6b-in-cancers-current-progress-and-future-perspectives
#12
Zhan Gang Xiao, Jing Shen, Lin Zhang, Long Fei Li, Ming Xing Li, Wei Hu, Zhi Jie Li, Chi Hin Cho
Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer...
July 24, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27456830/role-of-serum-amyloid-a-granulocyte-macrophage-colony-stimulating-factor-and-bone-marrow-granulocyte-monocyte-precursor-expansion-in-segmented-filamentous-bacterium-mediated-protection-from-entamoeba-histolytica
#13
Stacey L Burgess, Mahmoud Saleh, Carrie A Cowardin, Erica Buonomo, Zannatun Noor, Koji Watanabe, Mayuresh Abhyankar, Stephane Lajoie, Marsha Wills-Karp, William A Petri
Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of bone marrow in SFB-mediated protection. Transient gut colonization with SFB or SAA administration alone transiently increased the H3K27 histone demethylase Jmjd3, persistently increased bone marrow Csf2ra expression and granulocyte monocyte precursors (GMPs), and protected from ameba infection...
October 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27425890/jmjd3-mediates-blood-spinal-cord-barrier-disruption-after-spinal-cord-injury-by-regulating-mmp-3-and-mmp-9-expressions
#14
Jee Y Lee, Won H Na, Hae Y Choi, Kwang H Lee, Bong G Ju, Tae Y Yune
The disruption of the blood-spinal cord barrier (BSCB) by matrix metalloprotease (MMP) activation is a detrimental event that leads to blood cell infiltration, inflammation, and apoptosis, thereby contributing to permanent neurological disability after spinal cord injury (SCI). However, the molecular mechanisms underlying Mmp gene regulation have not been fully elucidated. Here, we demonstrated the critical role of histone H3K27 demethylase Jmjd3 in the regulation of Mmp gene expression and BSCB disruption using in vitro cellular and in vivo animal models...
November 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27388528/h3k27me3-demethylases-regulate-in-vitro-chondrogenesis-and-chondrocyte-activity-in-osteoarthritis
#15
Clarence Yapp, Andrew J Carr, Andrew Price, Udo Oppermann, Sarah J B Snelling
BACKGROUND: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. METHODS: We used a high-content screen to assess the effect of epigenetic modifying compounds on collagen output during chondrogenesis of monolayer human mesenchymal stem cells (MSCs)...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27384759/the-maternal-effect-genes-utx-and-jmjd3-play-contrasting-roles-in-mus-musculus-preimplantation-embryo-development
#16
Lei Yang, Li-Shuang Song, Xue-Fei Liu, Qing Xia, Li-Ge Bai, Li Gao, Guang-Qi Gao, Yu Wang, Zhu-Ying Wei, Chun-Ling Bai, Guang-Peng Li
During the process of embryonic development in mammals, epigenetic modifications must be erased and reconstructed. In particular, the trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcriptional repression and contributes to the maintenance of the pluripotent embryos. In this study, we determined that the global levels of the H3K27me3 marker were elevated in MII oocyte chromatin and decrease to minimal levels at the 8-cell and morula stages. When the blastocyst hatched, H3K27me3 was re-established in the inner cell mass...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27253528/cyclical-dna-methylation-and-histone-changes-are-induced-by-lps-to-activate-cox-2-in-human-intestinal-epithelial-cells
#17
Tiziana Angrisano, Raffaela Pero, Mariarita Brancaccio, Lorena Coretti, Ermanno Florio, Antonio Pezone, Viola Calabrò, Geppino Falco, Simona Keller, Francesca Lembo, Vittorio Enrico Avvedimento, Lorenzo Chiariotti
Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation...
2016: PloS One
https://www.readbyqxmd.com/read/27224921/screen-identified-selective-inhibitor-of-lysine-demethylase-5a-blocks-cancer-cell-growth-and-drug-resistance
#18
Molly Gale, Joyce Sayegh, Jian Cao, Michael Norcia, Peter Gareiss, Denton Hoyer, Jane S Merkel, Qin Yan
Lysine demethylase 5A (KDM5A/RBP2/JARID1A) is a histone lysine demethylase that is overexpressed in several human cancers including lung, gastric, breast and liver cancers. It plays key roles in important cancer processes including tumorigenesis, metastasis, and drug tolerance, making it a potential cancer therapeutic target. Chemical tools to analyze KDM5A demethylase activity are extremely limited as available inhibitors are not specific for KDM5A. Here, we characterized KDM5A using a homogeneous luminescence-based assay and conducted a screen of about 9,000 small molecules for inhibitors...
May 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27207907/acute-and-chronic-electroconvulsive-seizures-ecs-differentially-regulate-the-expression-of-epigenetic-machinery-in-the-adult-rat-hippocampus
#19
Madhavi Pusalkar, Shreya Ghosh, Minal Jaggar, Basma Fatima Anwar Husain, Sanjeev Galande, Vidita A Vaidya
BACKGROUND: Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. METHODS: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis...
May 17, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27151432/histone-demethylases-in-physiology-and-cancer-a-tale-of-two-enzymes-jmjd3-and-utx
#20
REVIEW
Kelly Marie Arcipowski, Carlos Alberto Martinez, Panagiotis Ntziachristos
Gene regulation is fine-tuned by a dynamic balance between transcriptionally activating and repressive modifications of histone tails. It has been well-established that lysine and arginine methylation can be reversed by two groups of evolutionarily conserved enzymes known as histone demethylases, which have been shown to play critical roles in development, differentiation and diseases like cancer. Recent work has demonstrated demethylase-independent functions of these proteins, highlighting the complex mechanisms by which these proteins exert their effects on gene expression...
February 2016: Current Opinion in Genetics & Development
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