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epigenetic regulation

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https://www.readbyqxmd.com/read/29036709/deep-learning-of-the-splicing-epi-genetic-code-reveals-a-novel-candidate-mechanism-linking-histone-modifications-to-esc-fate-decision
#1
Yungang Xu, Yongcui Wang, Jiesi Luo, Weiling Zhao, Xiaobo Zhou
Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA processing to increase transcriptome and proteome diversity. Comprehensively decoding these regulatory mechanisms holds promise in getting deeper insights into a variety of biological contexts involving in AS, such as development and diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic stem cell (hESC) differentiation by integrating heterogeneous features of genomic sequences, 16 histone modifications with a multi-label deep neural network...
September 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036683/cr2cancer-a-database-for-chromatin-regulators-in-human-cancer
#2
Beibei Ru, Jianlong Sun, Yin Tong, Ching Ngar Wong, Aditi Chandra, Acacia Tsz So Tang, Larry Ka Yue Chow, Wai Lam Wun, Zarina Levitskaya, Jiangwen Zhang
Chromatin regulators (CRs) can dynamically modulate chromatin architecture to epigenetically regulate gene expression in response to intrinsic and extrinsic signalling cues. Somatic alterations or misexpression of CRs might reprogram the epigenomic landscape of chromatin, which in turn lead to a wide range of common diseases, notably cancer. Here, we present CR2Cancer, a comprehensive annotation and visualization database for CRs in human cancer constructed by high throughput data analysis and literature mining...
October 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036320/detect-differentially-methylated-regions-using-non-homogeneous-hidden-markov-model-for-methylation-array-data
#3
Linghao Shen, Jun Zhu, Shuo-Yen Robert Li, Xiaodan Fan
Motivation: DNA methylation is an important epigenetic mechanism in gene regulation and the detection of differentially methylated regions (DMRs) is enthralling for many disease studies. There are several aspects that we can improve over existing DMR detection methods: (i) methylation statuses of nearby CpG sites are highly correlated, but this fact has seldom been modelled rigorously due to the uneven spacing; (ii) it is practically important to be able to handle both paired and unpaired samples; and (iii) the capability to detect DMRs from a single pair of samples is demanded...
July 20, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29036316/the-role-of-small-rna-based-epigenetic-silencing-for-purifying-selection-on-transposable-elements-in-capsella-grandiflora
#4
Robert Horvath, Tanja Slotte
To avoid negative effects of transposable element (TE) proliferation, plants epigenetically silence TEs using a number of mechanisms, including RNA-directed DNA methylation. These epigenetic modifications can extend outside the boundaries of TE insertions and lead to silencing of nearby genes, resulting in a trade-off between TE silencing and interference with nearby gene regulation. Therefore, purifying selection is expected to remove silenced TE insertions near genes more efficiently and prevent their accumulation within a population...
September 27, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29036193/gestational-age-related-patterns-of-amot-methylation-are-revealed-in-preterm-infant-endothelial-progenitors
#5
Giovanna Vinci, Christophe Buffat, Stéphanie Simoncini, Farid Boubred, Isabelle Ligi, Florent Dumont, Bernard Le Bonniec, Thierry Fournier, Daniel Vaiman, Françoise Dignat-George, Umberto Simeoni
OBJECTIVE: Preterm birth is associated with altered angiogenesis and with increased risk of cardiovascular dysfunction and hypertension at adulthood. We previously demonstrated that in preterm newborns circulating cord blood endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are reduced in number and display altered angiogenic properties. Altered angiogenic function was associated with a decreased expression of pro-angiogenic genes, among which the AMOT gene which is a strong positive regulator of angiogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/29035547/pharmacokinetics-and-pharmacodynamics-of-the-triterpenoid-ursolic-acid-in-regulating-the-anti-oxidant-anti-inflammatory-and-epigenetic-gene-responses-in-rat-leukocytes
#6
Chengyue Zhang, Chao Wang, Wenji Li, Renyi Wu, Yue Guo, David Cheng, Yuqing Yang, Ioannis P Androulakis, Ah-Ng Kong
The triterpenoid ursolic acid (UA) has been proposed as a potential cancer chemopreventive agent in many preclinical and clinical studies. In the present work, we aimed to characterize the pharmacokinetics (PK) of UA and to quantitatively assess the anti-oxidative and anti-inflammatory effects of UA, which are potentially linked to its chemopreventive efficacy. UA was administered intravenously (i.v., 20 mg/kg) or by oral gavage (100 mg/kg) to male Sprague-Dawley rats, and blood samples were collected at a series of designated time points...
October 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29035388/a-novel-her2-gene-body-enhancer-contributes-to-her2-expression
#7
Q Liu, M V Kulak, N Borcherding, P K Maina, W Zhang, R J Weigel, H H Qi
The transcriptional regulation of the human epidermal growth factor receptor-2 (HER2) contributes to an enhanced HER2 expression in HER2-positive breast cancers with HER2 gene amplification and HER2-low or HER2-negative breast cancers following radiotherapy or endocrine therapy, and this drives tumorigenesis and the resistance to therapy. Epigenetic mechanisms are critical for transcription regulation, however, such mechanisms in the transcription regulation of HER2 are limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and acetylated histone 3 lysine 9 (H3K9ac) at the HER2 promoter region...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#8
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29035367/targeting-glioma-stem-cells-through-combined-bmi1-and-ezh2-inhibition
#9
Xun Jin, Leo J Y Kim, Qiulian Wu, Lisa C Wallace, Briana C Prager, Tanwarat Sanvoranart, Ryan C Gimple, Xiuxing Wang, Stephen C Mack, Tyler E Miller, Ping Huang, Claudia L Valentim, Qi-Gang Zhou, Jill S Barnholtz-Sloan, Shideng Bao, Andrew E Sloan, Jeremy N Rich
Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis. Here, we demonstrate that these histological features are associated with distinct transcriptional programs, with vascular regions showing a proneural profile, and hypoxic regions showing a mesenchymal pattern. As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated EZH2, whereas mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress due to downregulation of the E3 ligase RNF144A...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29035278/hdac3-regulates-lymphovenous-and-lymphatic-valve-formation
#10
Harish P Janardhan, Zachary J Milstone, Masahiro Shin, Nathan D Lawson, John F Keaney, Chinmay M Trivedi
Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve development; yet the epigenetic modifiers underlying lymphatic valve morphogenesis remain elusive. Here, we showed that during mouse development, the histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of both lymphovenous valves, which maintain the separation of the blood and lymphatic vascular systems, and the lymphatic valves. Endothelium-specific ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective lymphovenous valve morphogenesis, improper lymphatic drainage, defective lymphatic valve maturation, and complete lethality...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29034500/how-communication-between-nucleosomes-enables-spreading-and-epigenetic-memory-of-histone-modifications
#11
REVIEW
Fabian Erdel
Nucleosomes "talk" to each other about their modification state to form extended domains of modified histones independently of the underlying DNA sequence. At the same time, DNA elements promote modification of nucleosomes in their vicinity. How do these site-specific and histone-based activities act together to regulate spreading of histone modifications along the genome? How do they enable epigenetic memory to preserve cell identity? Many models for the dynamics of repressive histone modifications emphasize the role of strong positive feedback loops, which reinforce histone modifications by recruiting histone modifiers to preexisting modifications...
October 16, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29033955/multilevel-regulation-of-abiotic-stress-responses-in-plants
#12
REVIEW
David C Haak, Takeshi Fukao, Ruth Grene, Zhihua Hua, Rumen Ivanov, Giorgio Perrella, Song Li
The sessile lifestyle of plants requires them to cope with stresses in situ. Plants overcome abiotic stresses by altering structure/morphology, and in some extreme conditions, by compressing the life cycle to survive the stresses in the form of seeds. Genetic and molecular studies have uncovered complex regulatory processes that coordinate stress adaptation and tolerance in plants, which are integrated at various levels. Investigating natural variation in stress responses has provided important insights into the evolutionary processes that shape the integrated regulation of adaptation and tolerance...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29033456/the-dna-methyltransferase-family-a-versatile-toolkit-for-epigenetic-regulation
#13
REVIEW
Frank Lyko
The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes that have a central role in epigenetic gene regulation. Recent studies have shown that the functions of the canonical DNMT enzymes - DNMT1, DNMT3A and DNMT3B - go beyond their traditional roles of establishing and maintaining DNA methylation patterns. This Review analyses how molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation...
October 16, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29033307/neurog1-regulates-cdk2-to-promote-proliferation-in-otic-progenitors
#14
Zhichao Song, Azadeh Jadali, Bernd Fritzsch, Kelvin Y Kwan
Loss of spiral ganglion neurons (SGNs) significantly contributes to hearing loss. Otic progenitor cell transplantation is a potential strategy to replace lost SGNs. Understanding how key transcription factors promote SGN differentiation in otic progenitors accelerates efforts for replacement therapies. A pro-neural transcription factor, Neurogenin1 (Neurog1), is essential for SGN development. Using an immortalized multipotent otic progenitor (iMOP) cell line that can self-renew and differentiate into otic neurons, NEUROG1 was enriched at the promoter of cyclin-dependent kinase 2 (Cdk2) and neurogenic differentiation 1 (NeuroD1) genes...
October 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#15
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29032501/epigenetic-regulators-multifunctional-proteins-modulating-hypoxia-inducible-factor-%C3%AE-protein-stability-and-activity
#16
REVIEW
Weibo Luo, Yingfei Wang
The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor governing a transcriptional program in response to reduced O2 availability in metazoans. It contributes to physiology and pathogenesis of many human diseases through its downstream target genes. Emerging studies have shown that the transcriptional activity of HIF is highly regulated at multiple levels and the epigenetic regulators are essential for HIF-mediated transactivation. In this review, we will discuss the comprehensive regulation of HIF transcriptional activity by different types of epigenetic regulators...
October 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29032046/past-present-and-future-of-genetic-research-in-borderline-personality-disorder
#17
REVIEW
Anahita Bassir Nia, Matthew C Eveleth, Jonathan M Gabbay, Yonis J Hassan, Bosi Zhang, M Mercedes Perez-Rodriguez
Borderline Personality Disorder (BPD) is a major mental illness with a lifetime prevalence of approximately 1-3%, characterized by a persistent pattern of instability in relationships, mood, impulse regulation, and sense of self. This results in impulsive self-damaging behavior, high suicide rates, and severe functional impairment. BPD has a complex, multifactorial etiology, resulting from an interaction among genetic and environmental substrates, and has moderate to high heritability based on twin and family studies...
September 12, 2017: Current Opinion in Psychology
https://www.readbyqxmd.com/read/29031162/dna-demethylation-activates-genes-in-seed-maternal-integument-development-in-rice-oryza-sativa-l
#18
Yifeng Wang, Haiyan Lin, Xiaohong Tong, Yuxuan Hou, Yuxiao Chang, Jian Zhang
DNA methylation is an important epigenetic modification that regulates various plant developmental processes. Rice seed integument determines the seed size. However, the role of DNA methylation in its development remains largely unknown. Here, we report the first dynamic DNA methylomic profiling of rice maternal integument before and after pollination by using a whole-genome bisulfite deep sequencing approach. Analysis of DNA methylation patterns identified 4238 differentially methylated regions underpin 4112 differentially methylated genes, including GW2, DEP1, RGB1 and numerous other regulators participated in maternal integument development...
September 27, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29030974/dopamine-transporter-gene-methylation-is-associated-with-nucleus-accumbens-activation-during-reward-processing-in-healthy-but-not-alcohol-dependent-individuals
#19
Christine Muench, Corinde E Wiers, Carlos R Cortes, Reza Momenan, Falk W Lohoff
BACKGROUND: Alcohol's reinforcement is mediated by dopamine signaling in the ventral striatum, which is modulated by the dopamine transporter (DAT). We hypothesized that methylomic variation in the DAT gene (SLC6A3) affects DAT expression thus contributing to differences in brain reward circuitry in individuals with alcohol dependence (ALC). METHODS: Blood from 45 recently detoxified ALC and 45 healthy control (HC) individuals was used to assess DNA methylation across 5 functional regions of SLC6A3...
October 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29030904/development-and-maintenance-of-the-brain-s-immune-toolkit-microglia-and-non-parenchymal-brain-macrophages
#20
REVIEW
Jose P Lopez-Atalaya, Katharine E Askew K, Amanda Sierra, Diego Gomez-Nicola
Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout the lifespan thanks to constant turnover. Microglia develop from yolk sac progenitors, later evolving through intermediate progenitors in a fine-tuned process in which intrinsic factors and external stimuli combine to progressively sculpt their cell-type specific transcriptional profiles...
October 14, 2017: Developmental Neurobiology
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