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https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#1
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29780165/a-medial-prefrontal-cortex-nucleus-acumens-corticotropin-releasing-factor-circuitry-for-neuropathic-pain-increased-susceptibility-to-opioid-reward
#2
Yuanzhong Kai, Yanhua Li, Tingting Sun, Weiwei Yin, Yu Mao, Jie Li, Wen Xie, Shi Chen, Likui Wang, Juan Li, Zhi Zhang, Wenjuan Tao
Recent studies have shown that persistent pain facilitates the response to morphine reward. However, the circuit mechanism underlying this process remains ambiguous. In this study, using chronic constriction injury (CCI) of the sciatic nerve in mice, we found that persistent neuropathic pain reduced the minimum number of morphine conditioning sessions required to induce conditioned place preference (CPP) behavior. This dose of morphine had no effect on the pain threshold. In the medial prefrontal cortex (mPFC), which is involved in both pain and emotion processing, corticotropin-releasing factor (CRF) expressing neuronal activity was increased in CCI mice...
May 21, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29774081/g9a-stimulates-crc-growth-by-inducing-p53-lys373-dimethylation-dependent-activation-of-plk1
#3
Jie Zhang, Yafang Wang, Yanyan Shen, Pengxing He, Jian Ding, Yi Chen
Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a...
2018: Theranostics
https://www.readbyqxmd.com/read/29745895/g9a-regulates-temporal-preimplantation-developmental-program-and-lineage-segregation-in-blastocyst
#4
Jan J Zylicz, Maud Borensztein, Frederick Ck Wong, Yun Huang, Caroline Lee, Sabine Dietmann, M Azim Surani
Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8-cell stage to promote timely repression of a subset of 4-cell stage-specific genes...
May 10, 2018: ELife
https://www.readbyqxmd.com/read/29720423/cutting-edge-the-histone-methyltransferase-g9a-is-required-for-silencing-of-helper-t-lineage-associated-genes-in-proliferating-cd8-t-cells
#5
Daniel J Verbaro, Nagisa Sakurai, Byungil Kim, Yoichi Shinkai, Takeshi Egawa
Helper versus cytotoxic T lineage decision in the thymus has been studied as a model for silencing of alternative lineage genes. Although the transcription factor RUNX3 is required for the initiation of Cd4 silencing in developing CD8 T cells, it is unknown how silencing of Cd4 and other helper T lineage genes is maintained. We show that the histone methyltransferase G9a is necessary for silencing helper T lineage genes in proliferating mouse CD8 T cells. Despite normal initial Cd4 downregulation, G9a-deficient CD8 T cells derepress Cd4 and other helper lineage genes during repeated division in lymphopenia or in response to tumor Ag...
May 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29650963/epigenetic-control-of-il-23-expression-in-keratinocytes-is-important-for-chronic-skin-inflammation
#6
Hui Li, Qi Yao, Alberto Garcia Mariscal, Xudong Wu, Justus Hülse, Esben Pedersen, Kristian Helin, Ari Waisman, Caroline Vinkel, Simon Francis Thomsen, Alexandra Avgustinova, Salvador Aznar Benitah, Paola Lovato, Hanne Norsgaard, Mette Sidsel Mortensen, Lone Veng, Björn Rozell, Cord Brakebusch
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29562667/vhl-and-hypoxia-signaling-beyond-hif-in-cancer
#7
REVIEW
Jing Zhang, Qing Zhang
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc...
March 19, 2018: Biomedicines
https://www.readbyqxmd.com/read/29555582/suberanilohydroxamic-acid-prevents-tgf-%C3%AE-1-induced-cox-2-repression-in-human-lung-fibroblasts-post-transcriptionally-by-tia-1-downregulation
#8
Alice Pasini, Oliver J Brand, Gisli Jenkins, Alan J Knox, Linhua Pang
Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE2 , is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE2 have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29553088/a-novel-mechanism-of-%C3%AE-irradiation-induced-il-6-production-mediated-by-p2y11-receptor-in-epidermal-keratinocytes
#9
Airi Ohsaki, Yuki Miyano, Rei Tanaka, Sei-Ichi Tanuma, Shuji Kojima, Mitsutoshi Tsukimoto
Skin inflammation is caused by excessive production of cytokines and chemokines in response to an external stimulus, such as radiation, but the mechanisms involved are not completely understood. Here, we report a novel mechanism of γ-irradiation-induced IL-6 production mediated by P2Y11 receptors in epidermal cells. After irradiation of HaCaT cells derived from human epidermal keratinocytes with 5 Gy of γ-rays (137 Cs : 0.78 Gy/min), IL-6 production was unchanged at 24 h after γ-irradiation, but was increased at 48 h...
March 16, 2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29531826/bix-01294-sensitizes-renal-cancer-caki-cells-to-trail-induced-apoptosis-through-downregulation-of-survivin-expression-and-upregulation-of-dr5-expression
#10
Seon Min Woo, Seung Un Seo, Kyoung-Jin Min, Taeg Kyu Kwon
BIX-01294 (BIX), a G9a histone methyltransferase inhibitor, has been reported for its anti-proliferative and anticancer activities against various cancer cell lines. In this study, we investigated whether BIX could sensitize TRAIL-mediated apoptosis in various cancer cells. Combined treatment with BIX and TRAIL markedly induced apoptosis in human renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MCF-7), and lung carcinoma (A549) cells. In contrast, BIX and TRAIL co-treatment did not induce apoptosis in normal cells, specifically mouse kidney cell (TCMK-1) and human skin fibroblast (HSF)...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29526734/combined-loss-of-jmjd1a-and-jmjd1b-reveals-critical-roles-for-h3k9-demethylation-in-the-maintenance-of-embryonic-stem-cells-and-early-embryogenesis
#11
Shunsuke Kuroki, Yuji Nakai, Ryo Maeda, Naoki Okashita, Mika Akiyoshi, Yutaro Yamaguchi, Satsuki Kitano, Hitoshi Miyachi, Ryuichiro Nakato, Kenji Ichiyanagi, Katsuhiko Shirahige, Hiroshi Kimura, Yoichi Shinkai, Makoto Tachibana
Histone H3 lysine 9 (H3K9) methylation is unevenly distributed in mammalian chromosomes. However, the molecular mechanism controlling the uneven distribution and its biological significance remain to be elucidated. Here, we show that JMJD1A and JMJD1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin. JMJD1A/JMJD1B-deficient embryos died soon after implantation accompanying epiblast cell death. Furthermore, combined loss of JMJD1A and JMJD1B caused perturbed expression of metabolic genes and rapid cell death in embryonic stem cells (ESCs)...
April 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29525533/maternal-green-tea-polyphenol-intake-during-lactation-attenuates-kidney-injury-in-high-fat-diet-fed-male-offspring-programmed-by-maternal-protein-restriction-in-rats
#12
Saori Kataoka, Toshio Norikura, Shin Sato
Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation...
February 9, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29519735/inhibition-of-histone-lysine-methyltransferases-g9a-and-glp-by-ejection-of-structural-zn-ii
#13
Danny C Lenstra, Abbas H K Al Temimi, Jasmin Mecinović
Histone lysine methyltransferases G9a and GLP are validated targets for the development of new epigenetic drugs. Most, if not all, inhibitors of G9a and GLP target the histone substrate binding site or/and the S-adenosylmethionine cosubstrate binding site. Here, we report an alternative approach for inhibiting the methyltransferase activity of G9a and GLP. For proper folding and enzymatic activity, G9a and GLP contain structural zinc fingers, one of them being adjacent to the S-adenosylmethionine binding site...
April 15, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29504609/macrophage-migration-inhibitory-factor-mediates-peripheral-nerve-injury-induced-hypersensitivity-by-curbing-dopaminergic-descending-inhibition
#14
Xian Wang, Shaolei Ma, Haibo Wu, Xiaofeng Shen, Shiqin Xu, Xirong Guo, Maria L Bolick, Shizheng Wu, Fuzhou Wang
Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory...
February 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29498708/identification-and-characterizations-of-novel-selective-histone-methyltransferase-set7-inhibitors-by-scaffold-hopping-and-2d-molecular-fingerprint-based-similarity-search
#15
Hong Ding, Wen Chao Lu, Jun Chi Hu, Yu-Chih Liu, Chen Hua Zhang, Fu Lin Lian, Nai Xia Zhang, Fan Wang Meng, Cheng Luo, Kai Xian Chen
SET7, serving as the only histone methyltransferase that monomethylates 'Lys-4' of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What's more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29467226/e4bp4-nfil3-modulates-the-epigenetically-repressed-ras-effector-rassf8-function-through-histone-methyltransferases
#16
Isai Pratha Karthik, Pavitra Desai, Sudarkodi Sukumar, Aleksandra Dimitrijevic, Krishnaraj Rajalingam, Sundarasamy Mahalingam
RAS proteins are major human oncogenes, and most of the studies are focused on enzymatic RAS effectors. Recently, nonenzymatic RAS effectors (RASSF, RAS association domain family) have garnered special attention because of their tumor-suppressive properties in contrast to the oncogenic potential of the classical enzymatic RAS effectors. Whereas most members of RASSF family are deregulated by promoter hypermethylation, RASSF8 promoter remains unmethylated in many cancers but the mechanism(s) of its down-regulation remains unknown...
April 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29459631/biochemical-validation-of-ehmt1-missense-mutations-in-kleefstra-syndrome
#17
Ayumi Yamada, Chikako Shimura, Yoichi Shinkai
Kleefstra syndrome (KS) (9q34 deletion syndrome) is a rare autosomal dominant disorder characterized by intellectual disability, frequently coupled with a spectrum of complex physical and clinical manifestations. As the euchromatic histone methyltransferase-1 gene (EHMT1, GLP, or KMT1D) within the 9q34 region is deleted or mutated in most of the individuals with KS, its absence or defect in one allele is speculated to cause the major symptoms of the syndrome. Most of the EHMT1 mutations are frameshift or nonsense mutations, but two individuals with KS were reported to possess EHMT1 missense mutations...
May 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29449539/g9a-promotes-gastric-cancer-metastasis-by-upregulating-itgb3-in-a-set-domain-independent-manner
#18
Lei Hu, Ming-de Zang, He-Xiao Wang, Bao-Gui Zhang, Zhen-Qiang Wang, Zhi-Yuan Fan, Huo Wu, Jian-Fang Li, Li-Ping Su, Min Yan, Zhi-Qiang Zhu, Qiu-Meng Yang, Qiang Huang, Bing-Ya Liu, Zheng-Gang Zhu
Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29426472/nuclear-delivery-of-parasite-cdg2_flc_0220-rna-transcript-to-epithelial-cells-during-cryptosporidium-parvum-infection-modulates-host-gene-transcription
#19
Guang-Hui Zhao, Ai-Yu Gong, Yang Wang, Xin-Tian Zhang, Min Li, Nicholas W Mathy, Xian-Ming Chen
Intestinal infection by the zoonotic protozoan, Cryptosporidium parvum, causes significant alterations in the gene expression profile in host epithelial cells. The molecular mechanisms of how C. parvum may modulate host cell gene transcription and the pathological significance of such alterations are largely unclear. Previous studies demonstrate that a panel of parasite RNA transcripts are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the impact of host delivery of C...
February 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29417943/inhibition-of-the-g9a-glp-histone-methyltransferase-complex-modulates-anxiety-related-behavior-in-mice
#20
Dong-Yao Wang, Joel Kosowan, James Samsom, Laura Leung, Kai-Lai Zhang, Ying-Xiang Li, Yan Xiong, Jian Jin, Arturas Petronis, Gabriel Oh, Albert H C Wong
Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets...
February 8, 2018: Acta Pharmacologica Sinica
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