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epigenetic regulation

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https://www.readbyqxmd.com/read/28548959/identification-of-the-histone-lysine-demethylase-kdm4a-jmjd2a-as-a-novel-epigenetic-target-in-m1-macrophage-polarization-induced-by-oxidized-ldl
#1
Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M Hermann, Thorsten R Döppner, Fengyan Jin, Yun Dai, Jiang Wu
Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548935/hdac4-stimulates-mrtf-a-expression-and-drives-fibrogenesis-in-hepatic-stellate-cells-by-targeting-mir-206
#2
Xinrui Han, Chenzhi Hao, Luyang Li, Jianfei Li, Mingming Fang, Yuanlin Zheng, Jun Lu, Ping Li, Yong Xu
Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrogenesis. We have previously shown that the transcriptional modulator MRTF-A contributes to liver fibrosis by programming epigenetic activation of HSCs. In the present study we investigated the mechanism whereby MRTF-A expression is regulated in this process. We report here that MRTF-A protein levels, but not mRNA levels, were up-regulated in vivo in the livers of mice induced to develop hepatic fibrosis. Pro-fibrogenic stimuli (TGF-β and PDGF-BB) also activated MRTF-A expression post-transcriptionally in vitro in cultured HSCs...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548660/transcriptomic-and-micrornaomic-profiling-reveals-multi-faceted-mechanisms-to-cope-with-phosphate-stress-in-a-dinoflagellate
#3
Xinguo Shi, Xin Lin, Ling Li, Meizhen Li, Brian Palenik, Senjie Lin
Although gene regulation can occur at both transcriptional and epigenetic (microRNA) levels, combined transcriptomic and microRNAomic responses to environmental stress are still largely unexplored for marine plankton. Here, we conducted transcriptome and microRNAome sequencing for Prorocentrum donghaiense to understand the molecular mechanisms by which this dinoflagellate copes with phosphorus (P) deficiency. Under P-depleted conditions, G1/S specific cyclin gene was markedly downregulated, consistent with growth inhibition, and genes related to dissolved organic phosphorus (DOP) hydrolysis, carbon fixation, nitrate assimilation, glycolysis, and cellular motility were upregulated...
May 26, 2017: ISME Journal
https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#4
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
May 26, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28546856/epigenetic-regulation-of-runx2-transcription-and-osteoblast-differentiation-by-nicotinamide-phosphoribosyltransferase
#5
Min Ling, Peixin Huang, Shamima Islam, Daniel P Heruth, Xuanan Li, Li Qin Zhang, Ding-You Li, Zhaohui Hu, Shui Qing Ye
BACKGROUND: Bone degenerative disorders like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Although there are studies suggesting that metabolic changes occur with stem cell differentiation, the molecular mechanisms governing energy metabolism and epigenetic modification are not understood fully. Here we reported the key role of nicotinamide phosphoribosyltransferase (Nampt), which is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide, in the osteogenic differentiation of bone marrow stromal cells...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28546787/pepsinogen-c-expression-regulation-and-its-relationship-with-cancer
#6
REVIEW
Shixuan Shen, Jingyi Jiang, Yuan Yuan
Pepsinogen C (PGC) belongs to the aspartic protease family and is secreted by gastric chief cells. PGC could be activated to pepsin C and digests polypeptides and amino acids, but as a zymogen PGC's functions is unclear. In normal physiological conditions, PGC is initially detected in the late embryonic stage and is mainly expressed in gastric mucosa. The in situ expression of PGC in gastric mucosa is decreased considerably in the process of superficial gastritis → atrophic gastritis → gastric cancer (GC), proving that PGC is a comparatively ideal negative marker of GC...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28546713/current-concepts-of-epigenetics-in-testicular-cancer
#7
REVIEW
Alfredo Harb-De la Rosa, Meenakkshy Manoharan, Ahmed Saeed Goolam
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure...
June 2017: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28546484/complete-genome-sequence-of-moraxella-catarrhalis-strain-ccri-195me-isolated-from-the-middle-ear
#8
Aimee Tan, Luke V Blakeway, Lauren O Bakaletz, Matthew Boitano, Tyson A Clark, Jonas Korlach, Michael P Jennings, Ian R Peak, Kate L Seib
Moraxella catarrhalis is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we report the complete genome sequence of M. catarrhalis strain CCRI-195ME, which contains the phase-variable epigenetic regulator ModM3.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#9
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545737/microrna-146a-governs-fibroblast-activation-and-joint-pathology-in-arthritis
#10
Victoria Saferding, Antonia Puchner, Eliana Goncalves-Alves, Melanie Hofmann, Michael Bonelli, Julia S Brunner, Emine Sahin, Birgit Niederreiter, Silvia Hayer, Hans P Kiener, Elisa Einwallner, Ramzi Nehmar, Raphael Carapito, Philippe Georgel, Marije I Koenders, Mark Boldin, Gernot Schabbauer, Mariola Kurowska-Stolarska, Günter Steiner, Josef S Smolen, Kurt Redlich, Stephan Blüml
Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation...
May 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28545587/type-2-diabetes-and-obesity-induce-similar-transcriptional-reprogramming-in-human-myocytes
#11
Leif Väremo, Tora Ida Henriksen, Camilla Scheele, Christa Broholm, Maria Pedersen, Mathias Uhlén, Bente Klarlund Pedersen, Jens Nielsen
BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor on genome-wide transcription...
May 25, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28545453/genome-wide-methylation-analysis-reveals-differentially-methylated-loci-that-are-associated-with-an-age-dependent-increase-in-bovine-fibroblast-response-to-lps
#12
Filiz T Korkmaz, David E Kerr
BACKGROUND: Differences in DNA methylation are known to contribute to the development of immune-related disorders in humans but relatively little is known about how methylation regulates immune function in cattle. Utilizing whole-transcriptome analyses of bovine dermal fibroblasts, we have previously identified an age and breed-dependent up-regulation of genes within the toll-like receptor 4 (TLR4) pathway that correlates with enhanced fibroblast production of IL-8 in response to lipopolysaccharide (LPS)...
May 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28545252/cpg-and-non-cpg-methylation-in-epigenetic-gene-regulation-and-brain-function
#13
REVIEW
Hyun Sik Jang, Woo Jung Shin, Jeong Eon Lee, Jeong Tae Do
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells...
May 23, 2017: Genes
https://www.readbyqxmd.com/read/28545238/epigenetic-strategies-to-boost-cancer-immunotherapies
#14
REVIEW
Maria J Barrero
Recently, immunotherapeutic approaches have shown impressive responses in a subset of cancer patients. However, the rate of success is low and a large percentage of treated patients do not experience clinical benefits. Therefore, additional strategies are needed to improve responses and select responsive patients. Emerging data suggest that epigenetic drugs can improve the responses to immunotherapy. Understanding the mechanisms of resistance to immunotherapy and the epigenetic events that take place during immune evasion is critical to providing a rational combined use of immunotherapies and epigenetic drugs...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545165/highly-recurrent-h3f3a-mutations-with-additional-epigenetic-regulator-alterations-in-giant-cell-tumor-of-bone
#15
Koichi Ogura, Fumie Hosoda, Hiromi Nakamura, Natsuko Hama, Yasushi Totoki, Akihiko Yoshida, Shoko Ohashi, Hirofumi Rokutan, Erina Takai, Shinichi Yachida, Akira Kawai, Sakae Tanaka, Tatsuhiro Shibata
Recurrent H3F3A and IDH2 mutations have been reported in giant cell tumor of bone (GCTB). However, the reported incidences have varied, and other molecular genetic alterations have not been identified due to the small number of cases analyzed with comprehensive methods. Moreover, the relative sensitivities of Sanger sequencing and next-generation sequencing (NGS) for the detection of H3F3A mutations in DNA extracted from archival formalin-fixed paraffin-embedded (FFPE) for clinical diagnosis have not been assessed...
May 25, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28543390/the-effect-of-ebv-on-wif1-nlk-and-apc-gene-methylation-and-expression-in-gastric-carcinoma-and-nasopharyngeal-cancer
#16
Zhenzhen Zhao, Wen Liu, Jincheng Liu, Jiayi Wang, Bing Luo
Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers. DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation and expression in gastric carcinoma and nasopharyngeal cancer. METHODS: The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines...
May 23, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28542476/functional-interaction-between-co-expressed-mage-a-proteins
#17
Julieta E Laiseca, María F Ladelfa, Javier Cotignola, Leticia Y Peche, Franco A Pascucci, Bryan A Castaño, Mario D Galigniana, Claudio Schneider, Martin Monte
MAGE-A (Melanoma Antigen Genes-A) are tumor-associated proteins with expression in a broad spectrum of human tumors and normal germ cells. MAGE-A gene expression and function are being increasingly investigated to better understand the mechanisms by which MAGE proteins collaborate in tumorigenesis and whether their detection could be useful for disease prognosis purposes. Alterations in epigenetic mechanisms involved in MAGE gene silencing cause their frequent co-expression in tumor cells. Here, we have analyzed the effect of MAGE-A gene co-expression and our results suggest that MageA6 can potentiate the androgen receptor (AR) co-activation function of MageA11...
2017: PloS One
https://www.readbyqxmd.com/read/28541657/chemical-modulation-of-protein-o-glcnacylation-via-ogt-inhibition-promotes-human-neural-cell-differentiation
#18
Lissette M Andres, Ian W Blong, Angela C Evans, Neil G Rumachik, Teppei Yamaguchi, Nam D Pham, Pamela Thompson, Jennifer J Kohler, Carolyn R Bertozzi
The enzymes that determine protein O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), act on key transcriptional and epigenetic regulators and both are abundantly expressed in the brain. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc)...
May 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28541567/dna-methylation-and-small-interference-rnas-participate-in-the-regulation-of-mads-box-genes-involved-in-dormancy-in-sweet-cherry-prunus-avium-l
#19
Karin Rothkegel, Evelyn Sánchez, Christian Montes, Macarena Greve, Sebastián Tapia, Soraya Bravo, Humberto Prieto, Andréa Miyasaka Almeida
Epigenetic modifications can yield information about connections between genotype, phenotype variation and environmental conditions. Bud dormancy release in temperate perennial fruit trees depends on internal and environmental signals such as cold accumulation and photoperiod. Previous investigations have noted the participation of epigenetic mechanisms in the control of this physiological process. We examined whether epigenetic modifications were modulated in MADS-box genes, potential candidates for the regulation of bud dormancy and flowering in sweet cherry (Prunus avium L...
May 24, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28541412/association-study-of-common-variants-in-pfn1-with-hypertension-in-a-han-chinese-population-a-case-control-study-and-a-follow-up-study
#20
Song Yang, Yanchun Chen, Chunlan Liu, Xianghai Zhao, Qian Zhuang, Junxiang Sun, Pengfei Wei, Hailong Zhao, Xiaotian Chen, Chong Shen
BACKGROUND: Animal researches reported that the dysfunction of profilin1 (PFN1) was involved in the physiological arterial stiffness and vascular remodeling linking to the etiology of hypertension (HT). This study mainly aims at evaluating the association of PFN1 and HT in a Han Chinese population. METHODS: A case-control study consisted of 2,012 HT cases and 2,210 controls was conducted and 2,116 participants from the healthy controls were further followed up for average 5...
May 24, 2017: American Journal of Hypertension
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