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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
#1
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
#2
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
#3
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...
July 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#4
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...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714978/%C3%AE-ketoglutarate-orchestrates-macrophage-activation-through-metabolic-and-epigenetic-reprogramming
#5
Pu-Ste Liu, Haiping Wang, Xiaoyun Li, Tung Chao, Tony Teav, Stefan Christen, Giusy Di Conza, Wan-Chen Cheng, Chih-Hung Chou, Magdalena Vavakova, Charlotte Muret, Koen Debackere, Massimiliano Mazzone, Hsien-Da Huang, Sarah-Maria Fendt, Julijana Ivanisevic, Ping-Chih Ho
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages...
July 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28630932/differential-intron-retention-in-jumonji-chromatin-modifier-genes-is-implicated-in-reptile-temperature-dependent-sex-determination
#6
Ira W Deveson, Clare E Holleley, James Blackburn, Jennifer A Marshall Graves, John S Mattick, Paul D Waters, Arthur Georges
In many vertebrates, sex of offspring is determined by external environmental cues rather than by sex chromosomes. In reptiles, for instance, temperature-dependent sex determination (TSD) is common. Despite decades of work, the mechanism by which temperature is converted into a sex-determining signal remains mysterious. This is partly because it is difficult to distinguish the primary molecular events of TSD from the confounding downstream signatures of sexual differentiation. We use the Australian central bearded dragon, in which chromosomal sex determination is overridden at high temperatures to produce sex-reversed female offspring, as a unique model to identify TSD-specific features of the transcriptome...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#7
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28575430/a-shot-in-the-dark-exposes-more-trees-in-the-forest-adding-a-histone-demethylase-jmjd3-and-rip-cre-neurons-to-the-coordination-of-female-reproductive-function
#8
https://www.readbyqxmd.com/read/28554742/immunohistochemical-investigation-of-topoii%C3%AE-h3k27me3-and-jmjd3-expressions-in-medulloblastoma
#9
Jing Chen, Junxia Zhao, Xiaofen Zhou, Shuang Liu, Yongxin Yan, Yanling Wang, Cuili Cao, Shou Han, Najing Zhou, Yannan Xu, Juan Zhao, Yunli Yan, Huixian Cui
Topoisomerase IIβ (topoIIβ) is a nuclear enzyme specifically expressed in neurons, and plays an important role in the development of the cerebellum. To date, the expression of topoIIβ protein in medulloblastoma (MB) has not been investigated. In this study, 16 MB specimens including 10 classical subtypes of MB and 6 desmoplastic subtypes of MB (DMB), along with 5 normal cerebellum samples, were obtained from clinics. With immunohistochemical staining, prominently expressed topoIIβ was seen in normal cerebellar tissues, while there was no or less pronounced staining in classical MB cells...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28529687/histone-demethylases-utx-and-jmjd3-are-required-for-nkt-cell-development-in-mice
#10
Daniel Northrup, Ryoji Yagi, Kairong Cui, William R Proctor, Chaochen Wang, Katarzyna Placek, Lance R Pohl, Rongfu Wang, Kai Ge, Jinfang Zhu, Keji Zhao
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28509866/hdac8-prevents-anthrax-lethal-toxin-induced-cell-cycle-arrest-through-silencing-pten-in-human-monocytic-thp-1-cells
#11
Soon-Duck Ha, Woohyun Cho, Sung Ouk Kim
Anthrax lethal toxin (LeTx) is a cytotoxic virulence factor that causes cell cycle arrest and cell death in various cell types. However, susceptibility to the cytotoxic effects varies depending on cell types. In proliferating monocytes, LeTx has only transient cytotoxic effects due to activation of the phosphoinositide 3-kinase (PI3K)-AKT-mediated adaptive responses. To date, the mechanism of LeTx in activating PI3K-AKT signaling axis is unknown. This study shows that the histone deacetylase 8 (HDAC8) is involved in activating PI3K-AKT signaling axis through down-regulating the phosphatase and tensin homolog 1 (PTEN) in human monocytic THP-1 cells...
May 16, 2017: Toxins
https://www.readbyqxmd.com/read/28487543/kdm6b-modulates-mapk-pathway-mediating-multiple-myeloma-cell-growth-and-survival
#12
H Ohguchi, T Harada, M Sagawa, S Kikuchi, Y-T Tai, P G Richardson, T Hideshima, K C Anderson
Recent studies have delineated cancer-type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM) cells; and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. Tumor necrosis factor-α or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting that KDM6B is regulated by NF-κB signaling in MM cells...
May 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28476540/epigenetic-and-transcriptional-modulation-of-wdr5-a-chromatin-remodeling-protein-in-huntington-s-disease-human-induced-pluripotent-stem-cell-hipsc-model
#13
Simona Baronchelli, Alberto La Spada, Aikaterini Ntai, Andrea Barbieri, Paola Conforti, Gloria Saccani Jotti, Serena Redaelli, Angela Bentivegna, Pasquale De Blasio, Ida Biunno
DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs. Subsequently, we focused on the methylation differences in a subcluster of genes related to Jumonji Domain Containing 3 (JMJD3), a demethylase that epigenetically regulates neuronal differentiation and activates neuronal progenitor associated genes, which are indispensable for neuronal fate acquisition...
May 2, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28430662/histone-demethylase-jmjd3-regulates-cd11a-expression-through-changes-in-histone-h3k27-tri-methylation-levels-in-cd4-t-cells-of-patients-with-systemic-lupus-erythematosus
#14
Heng Yin, Haijing Wu, Ming Zhao, Qing Zhang, Hai Long, Siqi Fu, Qianjin Lu
Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423536/jmjd3-suppresses-stem-cell-like-characteristics-in-breast-cancer-cells-by-downregulation-of-oct4-independently-of-its-demethylase-activity
#15
Jing Xun, Dekun Wang, Long Shen, Junbo Gong, Ruifang Gao, Lingfang Du, Antao Chang, Xiangrong Song, Rong Xiang, Xiaoyue Tan
Epigenetic regulator JMJD3 plays an important role in both tumor progression and somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem cell-like characteristics of breast cancer and its underlying mechanism involving stemness-related transcription factor Oct4. Our data revealed that, in breast cancer cells lines and an orthotopic xenograph mouse model of breast cancer, ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407004/epigenetically-repressing-human-cytomegalovirus-lytic-infection-and-reactivation-from-latency-in-thp-1-model-by-targeting-h3k9-and-h3k27-histone-demethylases
#16
Xin Gan, Haifeng Wang, Yanyan Yu, Wei Yi, Shanshan Zhu, En Li, Yu Liang
Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. In latent infection, the viral genome is suppressed in a heterochromatic state and viral gene transcription is silenced. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes...
2017: PloS One
https://www.readbyqxmd.com/read/28384648/regulation-of-the-jmjd3-kdm6b-histone-demethylase-in-glioblastoma-stem-cells-by-stat3
#17
Maureen M Sherry-Lynes, Sejuti Sengupta, Shreya Kulkarni, Brent H Cochran
The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect...
2017: PloS One
https://www.readbyqxmd.com/read/28372944/histone-demethylases-kdm6ba-and-kdm6bb-redundantly-promote-cardiomyocyte-proliferation-during-zebrafish-heart-ventricle-maturation
#18
Alexander A Akerberg, Astra Henner, Scott Stewart, Kryn Stankunas
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development...
June 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28338398/dexamethasone-suppresses-jmjd3-gene-activation-via-a-putative-negative-glucocorticoid-response-element-and-maintains-integrity-of-tight-junctions-in-brain-microvascular-endothelial-cells
#19
Wonho Na, Jee Y Shin, Jee Y Lee, Sangyun Jeong, Won-Sun Kim, Tae Y Yune, Bong-Gun Ju
The blood-brain barrier (BBB) exhibits a highly selective permeability to support the homeostasis of the central nervous system (CNS). The tight junctions in the BBB microvascular endothelial cells seal the paracellular space to prevent diffusion. Thus, disruption of tight junctions results in harmful effects in CNS diseases and injuries. It has recently been demonstrated that glucocorticoids have beneficial effects on maintaining tight junctions in both in vitro cell and in vivo animal models. In the present study, we found that dexamethasone suppresses the expression of JMJD3, a histone H3K27 demethylase, via the recruitment of glucocorticoid receptor α (GRα) and nuclear receptor co-repressor (N-CoR) to the negative glucocorticoid response element (nGRE) in the upstream region of JMJD3 gene in brain microvascular endothelial cells subjected to TNFα treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#20
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
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