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https://www.readbyqxmd.com/read/28446510/a-postprandial-fgf19-shp-lsd1-regulatory-axis%C3%A2-mediates-epigenetic-repression-of-hepatic%C3%A2-autophagy
#1
Sangwon Byun, Young-Chae Kim, Yang Zhang, Bo Kong, Grace Guo, Junichi Sadoshima, Jian Ma, Byron Kemper, Jongsook Kim Kemper
Lysosome-mediated autophagy is essential for cellular survival and homeostasis upon nutrient deprivation, but is repressed after feeding. Despite the emerging importance of transcriptional regulation of autophagy by nutrient-sensing factors, the role for epigenetic control is largely unexplored. Here, we show that Small Heterodimer Partner (SHP) mediates postprandial epigenetic repression of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late fed-state hormone, FGF19 (hFGF19, mFGF15)...
April 26, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#2
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
April 22, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28443478/role-of-oxidative-stress-in-epigenetic-modification-in-endometriosis
#3
Fuminori Ito, Yuki Yamada, Aiko Shigemitsu, Mika Akinishi, Hiroko Kaniwa, Ryuta Miyake, Shoichiro Yamanaka, Hiroshi Kobayashi
Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28440295/kdm3-epigenetically-controls-tumorigenic-potentials-of-human-colorectal-cancer-stem-cells-through-wnt-%C3%AE-catenin-signalling
#4
Jiong Li, Bo Yu, Peng Deng, Yingduan Cheng, Yongxin Yu, Kareena Kevork, Sivakumar Ramadoss, Xiangming Ding, Xinmin Li, Cun-Yu Wang
Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription...
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#5
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28435523/discovery-of-1-2-3-triazolo-4-5-d-pyrimidine-derivatives-as-novel-lsd1-inhibitors
#6
Zhong-Hua Li, Xue-Qi Liu, Peng-Fei Geng, Feng-Zhi Suo, Jin-Lian Ma, Bin Yu, Tao-Qian Zhao, Zhao-Qing Zhou, Chen-Xi Huang, Yi-Chao Zheng, Hong-Min Liu
Lysine specific demethylase 1 (LSD1) plays a pivotal role in regulating the lysine methylation. The aberrant overexpression of LSD1 has been reported to be involved in the progression of certain human malignant tumors. Abrogation of LSD1 with RNAi or small molecule inhibitors may lead to the inhibition of cancer proliferation and migration. Herein, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives were synthesized and evaluated for their LSD1 inhibitory effects. The structure-activity relationship studies (SARs) were conducted by exploring three regions of this scaffold, leading to the discovery of compound 27 as potent LSD1 inhibitor (IC50 = 0...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28434780/total-chemical-synthesis-of-methylated-analogues-of-histone-3-revealed-kdm4d-as-a-potential-regulator-of-h3k79me3
#7
Muhammad Jbara, Noga Guttmann-Raviv, Suman Kumar Maity, Nabieh Ayoub, Ashraf Brik
Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9...
April 12, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#8
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
April 4, 2017: Oncotarget
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
#9
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/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#10
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28429420/the-crystal-structure-of-a-new-o-demethylase-from-sphingobium-sp-strain-syk-6
#11
Ayaka Harada, Naofumi Kamimura, Koh Takeuchi, Hong Yang Yu, Eiji Masai, Toshiya Senda
In the cell, tetrahydrofolate derivatives with a C1 unit are utilized in various ways, such as for the synthesis of amino acids and nucleic acids. While tetrahydrofolate derivatives with the C1 unit are typically produced in the glycine cleavage system, Sphingobium sp. strain SYK-6, which can utilize lignin-derived aromatic compounds as a sole source of carbon and energy, lacks this pathway, probably due to its unique nutrient requirements. In this bacterium, tetrahydrofolate-dependent O-demethylases in catabolic pathways for lignin-derived aromatic compounds seem to be involved in the C1 metabolism...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28424474/molecular-epidemiology-and-azole-resistance-mechanism-study-of-candida-guilliermondii-from-a-chinese-surveillance-system
#12
Jing-Wei Cheng, Kang Liao, Timothy Kudinha, Shu-Ying Yu, Meng Xiao, He Wang, Fanrong Kong, Ying-Chun Xu
We studied the molecular epidemiology and mechanism of azole resistance of 164 C. guilliermondii isolates from a nationwide multi-center surveillance program. The isolates were identified by ITS gene sequencing, and the in vitro susceptibility to fluconazole and voriconazole was determined by broth microdilution method. The 14-α-demethylase gene ERG11 was amplified and sequenced, and microsatellite analysis was performed to study the genetic relatedness of the isolates. Amongst the 164 C. guilliermondii isolates, 15 (9...
April 19, 2017: Scientific Reports
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
#13
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/28423010/correction-the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#14
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0173713.].
2017: PloS One
https://www.readbyqxmd.com/read/28422711/melatonin-exerts-anti-oral-cancer-effect-via-suppressing-lsd1-in-patient-derived-tumor-xenograft-models
#15
Cheng-Yu Yang, Chih-Kung Lin, Chang-Huei Tsao, Cheng-Chih Hsieh, Gu-Jiun Lin, Kuo-Hsing Ma, Yi-Shing Shieh, Huey-Kang Sytwu, Yuan-Wu Chen
Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#16
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416745/stable-h3-peptide-was-delivered-by-gold-nanorods-to-inhibit-lsd1-activation-and-induce-human-mesenchymal-stem-cells-differentiation
#17
Xin Meng, Jianping Li, Minjuan Zheng, Lei Zuo, Chao Sun, Yongsheng Zhu, Ling Fang, Liwen Liu, Xiaodong Zhou
Recently, lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, regulates post-translational modifications and has great promise as new targets for cancer and other diseases. Moreover, the ability of LSD1 to induce the differentiation of stem cells has attracted great attention in biological fields. In this study, we designed LSD1 peptide inhibitor based on its substrate H3 peptide. Through introducing a disulfide bond to stabilize the native peptide into alpha helical structure, we get a peptide with higher cell permeability and stability compared to its parent form...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#18
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
April 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28415746/epigenetic-up-regulation-of-ribosome-biogenesis-and-more-aggressive-phenotype-triggered-by-the-lack-of-the-histone-demethylase-jhdm1b-in-mammary-epithelial-cells
#19
Alice Galbiati, Marianna Penzo, Maria Giulia Bacalini, Carmine Onofrillo, Ania Naila Guerrieri, Paolo Garagnani, Claudio Franceschi, Davide Treré, Lorenzo Montanaro
The alterations of ribosome biogenesis and protein synthesis play a direct role in the development of tumors. The accessibility and transcription of ribosomal genes is controlled at several levels, with their epigenetic regulation being one of the most important. Here we explored the JmjC domain-containing histone demethylase 1B (JHDM1B) function in the epigenetic control of rDNA transcription. Since JHDM1B is a negative regulator of gene transcription, we focused on the effects induced by JHDM1B knock-down (KD)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414096/lysine-specific-demethylase-1-lsd1-depletion-disrupts-monogenic-and-monoallelic-odorant-receptor-or-expression-in-an-olfactory-neuronal-cell-line
#20
Rutesh N Vyas, Diane Meredith, Robert P Lane
Function of the mammalian olfactory system depends on specialized olfactory sensory neurons (OSNs) that each express only one allele ("monoallelic") of one odorant receptor (OR) gene ("monogenic"). The lysine-specific demethylase-1 (LSD1) protein removes activating H3K4 or silencing H3K9 methylation marks in a variety of developmental contexts, and is thought to be important for proper OR regulation. Most of the focus in the field has been on a potential "activating" function for LSD1; e.g., in the demethylation of H3K9 associated with the expressed OR allele...
April 13, 2017: Molecular and Cellular Neurosciences
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