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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/28223506/intragenic-cpg-islands-play-important-roles-in-bivalent-chromatin-assembly-of-developmental-genes
#1
Sun-Min Lee, Jungwoo Lee, Kyung-Min Noh, Won-Young Choi, Sejin Jeon, Goo Taeg Oh, Jeongsil Kim-Ha, Yoonhee Jin, Seung-Woo Cho, Young-Joon Kim
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#2
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205577/epigenetic-signatures-of-invasive-status-in-populations-of-marine-invertebrates
#3
Alba Ardura, Anastasija Zaiko, Paloma Morán, Serge Planes, Eva Garcia-Vazquez
Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#4
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193886/improved-regulatory-element-prediction-based-on-tissue-specific-local-epigenomic-signatures
#5
Yupeng He, David U Gorkin, Diane E Dickel, Joseph R Nery, Rosa G Castanon, Ah Young Lee, Yin Shen, Axel Visel, Len A Pennacchio, Bing Ren, Joseph R Ecker
Accurate enhancer identification is critical for understanding the spatiotemporal transcriptional regulation during development as well as the functional impact of disease-related noncoding genetic variants. Computational methods have been developed to predict the genomic locations of active enhancers based on histone modifications, but the accuracy and resolution of these methods remain limited. Here, we present an algorithm, regulatory element prediction based on tissue-specific local epigenetic marks (REPTILE), which integrates histone modification and whole-genome cytosine DNA methylation profiles to identify the precise location of enhancers...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28157506/not-all-h3k4-methylations-are-created-equal-mll2-compass-dependency-in-primordial-germ-cell-specification
#6
Deqing Hu, Xin Gao, Kaixiang Cao, Marc A Morgan, Gloria Mas, Edwin R Smith, Andrew G Volk, Elizabeth T Bartom, John D Crispino, Luciano Di Croce, Ali Shilatifard
The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and epigenetic states at cis-regulatory elements. Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares epigenetic signatures of active enhancers. Our mechanistic studies reveal that association of Mll2's CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28157158/epigenetic-alterations-in-parathyroid-cancers
#7
REVIEW
Chiara Verdelli, Sabrina Corbetta
Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas...
February 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28153026/clinical-implications-of-genome-wide-dna-methylation-studies-in-acute-myeloid-leukemia
#8
REVIEW
Yan Li, Qingyu Xu, Na Lv, Lili Wang, Hongmei Zhao, Xiuli Wang, Jing Guo, Chongjian Chen, Yonghui Li, Li Yu
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. AML is a heterogeneous malignancy characterized by distinct genetic and epigenetic abnormalities. Recent genome-wide DNA methylation studies have highlighted an important role of dysregulated methylation signature in AML from biological and clinical standpoint. In this review, we will outline the recent advances in the methylome study of AML and overview the impacts of DNA methylation on AML diagnosis, treatment, and prognosis...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28146567/differential-dna-methylation-regions-in-adult-human-sperm-following-adolescent-chemotherapy-potential-for-epigenetic-inheritance
#9
Margarett Shnorhavorian, Stephen M Schwartz, Barbara Stansfeld, Ingrid Sadler-Riggleman, Daniel Beck, Michael K Skinner
BACKGROUND: The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a number of environmental exposures such as abnormal nutrition and toxicants can promote sperm epigenetic changes that impact offspring. METHODS: Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28134926/dna-methylation-heterogeneity-defines-a-disease-spectrum-in-ewing-sarcoma
#10
Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schönegger, Michael Schuster, Johanna Hadler, Didier Surdez, Delphine Guillemot, Eve Lapouble, Paul Freneaux, Jacqueline Champigneulle, Raymonde Bouvier, Diana Walder, Ingeborg M Ambros, Caroline Hutter, Eva Sorz, Ana T Amaral, Enrique de Álava, Katharina Schallmoser, Dirk Strunk, Beate Rinner, Bernadette Liegl-Atzwanger, Berthold Huppertz, Andreas Leithner, Gonzague de Pinieux, Philippe Terrier, Valérie Laurence, Jean Michon, Ruth Ladenstein, Wolfgang Holter, Reinhard Windhager, Uta Dirksen, Peter F Ambros, Olivier Delattre, Heinrich Kovar, Christoph Bock, Eleni M Tomazou
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma...
January 30, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28130639/global-epigenetic-profiling-identifies-methylation-subgroups-associated-with-recurrence-free-survival-in-meningioma
#11
Adriana Olar, Khalida M Wani, Charmaine D Wilson, Gelareh Zadeh, Franco DeMonte, David T W Jones, Stefan M Pfister, Erik P Sulman, Kenneth D Aldape
Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV)...
January 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28130225/cellular-model-of-colon-cancer-progression-reveals-signatures-of-mrnas-mirna-lncrnas-and-epigenetic-modifications-associated-with-metastasis
#12
Matjaz Rokavec, David Horst, Heiko Hermeking
Here we developed and comprehensively characterized a cellular model of colon cancer progression consisting of four defined derivatives of a colon cancer cell line that resulted from consecutive epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) and phenotypically recapitulate the metastatic cascade. Initial EMT was induced by prolonged exposure to IL-6, a cytokine also generated by the tumor-stroma. Genome-wide characterization of transcriptional (mRNA, miRNA, lncRNA) and epigenetic (DNA methylation, H3K4me3, H3K79me3, and H3K27me3 histone modifications) profiles of the cell derivatives, combined with correlative analyses of expression, methylation, and clinical data from the TCGA-COAD database gave insights into the molecular basis of their phenotypic changes...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28125717/epigenetic-alterations-affecting-transcription-factors-and-signaling-pathways-in-stromal-cells-of-endometriosis
#13
Iveta Yotova, Emily Hsu, Catherine Do, Aulona Gaba, Matthias Sczabolcs, Sabine Dekan, Lukas Kenner, Rene Wenzl, Benjamin Tycko
Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains...
2017: PloS One
https://www.readbyqxmd.com/read/28120717/understanding-epigenetic-alterations-in-alzheimer-s-and-parkinson-s-disease-towards-targeted-biomarkers-and-therapies
#14
Filippo Ciceri, David Rotllant, Tamara Maes
BACKGROUND: Alzheimer's and Parkinson's disease represent the two most common neurodegenerative disorders, affecting an increasing number of patients worldwide. Population ageing and lack of effective therapies and biomarkers strongly contribute to the socio-economical impact of these conditions. MESSAGE AND CONCLUSION: The aim of the review is to present a summary of the discoveries made on the epigenetics of Alzheimer's and Parkinson's disease, with a special focus on the recent advances towards the identification of new targeted therapies and biomarkers...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28111764/emerging-role-of-epigenetic-mechanisms-in-alcohol-addiction
#15
Tiffani D M Berkel, Subhash C Pandey
Alcohol use disorder (AUD) is a complex disorder with an array of persistent behavioral and neurochemical manifestations. Both genetic and environmental factors are known to contribute to the development of AUD, and recent studies on alcohol exposure and subsequent changes in gene expression suggest the importance of epigenetic mechanisms. In particular, histone modifications and DNA methylation have emerged as important regulators of gene expression and associated phenotypes of AUD. Given the therapeutic potential of epigenetic targets, this review aims to summarize the role of epigenetic regulation in our current understanding of AUD by evaluating known epigenetic signatures of brain regions critical to addictive behaviors in both animal and human studies throughout various stages of AUD...
January 23, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28111236/prevalence-of-prediabetes-risk-in-offspring-born-to-mothers-with-hyperandrogenism
#16
Shen Tian, Xian-Hua Lin, Yi-Meng Xiong, Miao-E Liu, Tian-Tian Yu, Min Lv, Wei Zhao, Gu-Feng Xu, Guo-Lian Ding, Chen-Ming Xu, Min Jin, Chun Feng, Yan-Ting Wu, Ya-Jing Tan, Qian Gao, Jian Zhang, Cheng Li, Jun Ren, Lu-Yang Jin, Bin Chen, Hong Zhu, Xue-Ying Zhang, Song-Chang Chen, Xin-Mei Liu, Ye Liu, Jun-Yu Zhang, Li Wang, Ping Zhang, Xiao-Jun Chen, Li Jin, Xi Chen, Yi-Cong Meng, Dan-Dan Wu, Hui Lin, Qian Yang, Cheng-Liang Zhou, Xin-Zhu Li, Yi-Yu Wang, Yu-Qian Xiang, Zhi-Wei Liu, Ling Gao, Lu-Ting Chen, Hong-Jie Pan, Rong Li, Fang-Hong Zhang, Lan-Feng Xing, Yi-Min Zhu, Christian Klausen, Peter C K Leung, Ju-Xue Li, Fei Sun, Jian-Zhong Sheng, He-Feng Huang
BACKGROUND: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. METHODS: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010...
January 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28102292/integrated-molecular-analysis-reveals-complex-interactions-between-genomic-and-epigenomic-alterations-in-esophageal-adenocarcinomas
#17
DunFa Peng, Yan Guo, Heidi Chen, Shilin Zhao, Kay Washington, TianLing Hu, Yu Shyr, Wael El-Rifai
The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096648/identification-of-genetic-and-epigenetic-variants-associated-with-breast-cancer-prognosis-by-integrative-bioinformatics-analysis
#18
Arunima Shilpi, Yingtao Bi, Segun Jung, Samir K Patra, Ramana V Davuluri
INTRODUCTION: Breast cancer being a multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. However, the task for the identification of these variances is complicated by the interplay between inherited genetic and epigenetic aberrations. Therefore, this study provides an extrapolate outlook to the sinister partnership between DNA methylation and single-nucleotide polymorphisms (SNPs) in relevance to the identification of prognostic markers in breast cancer...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28089908/human-aml-ipscs-reacquire-leukemic-properties-after-differentiation-and-model-clonal-variation-of-disease
#19
Mark P Chao, Andrew J Gentles, Susmita Chatterjee, Feng Lan, Andreas Reinisch, M Ryan Corces, Seethu Xavy, Jinfeng Shen, Daniel Haag, Soham Chanda, Rahul Sinha, Rachel M Morganti, Toshinobu Nishimura, Mohamed Ameen, Haodi Wu, Marius Wernig, Joseph C Wu, Ravindra Majeti
Understanding the relative contributions of genetic and epigenetic abnormalities to acute myeloid leukemia (AML) should assist integrated design of targeted therapies. In this study, we generated induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature...
December 26, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28088687/whole-genome-dna-methylation-profiling-identifies-epigenetic-signatures-of-uterine-carcinosarcoma
#20
Jing Li, Xiaoyun Xing, Daofeng Li, Bo Zhang, David G Mutch, Ian S Hagemann, Ting Wang
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma...
February 2017: Neoplasia: An International Journal for Oncology Research
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