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https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#1
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29759984/ndf-a-nucleosome-destabilizing-factor-that-facilitates-transcription-through-nucleosomes
#2
Jia Fei, Haruhiko Ishii, Marten A Hoeksema, Franz Meitinger, George A Kassavetis, Christopher K Glass, Bing Ren, James T Kadonaga
Our understanding of transcription by RNA polymerase II (Pol II) is limited by our knowledge of the factors that mediate this critically important process. Here we describe the identification of NDF, a nucleosome-destabilizing factor that facilitates Pol II transcription in chromatin. NDF has a PWWP motif, interacts with nucleosomes near the dyad, destabilizes nucleosomes in an ATP-independent manner, and facilitates transcription by Pol II through nucleosomes in a purified and defined transcription system as well as in cell nuclei...
May 14, 2018: Genes & Development
https://www.readbyqxmd.com/read/29755673/role-of-epigenetic-factors-in-the-selection-of-the-alternative-splicing-isoforms-of-human-kras-in-colorectal-cancer-cell-lines
#3
Ángela L Riffo-Campos, Francisco Gimeno-Valiente, Fernanda M Rodríguez, Andrés Cervantes, Gerardo López-Rodas, Luis Franco, Josefa Castillo
Mutation-driven activation of KRAS is crucial to cancer development. The human gene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Their different properties and oncogenic potential have been studied, but the mechanisms deciding the ratio 4A/4B are not known. To address this issue, the expression of the four KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116 and SW48 were further selected because they present the highest difference in the ratio 4A/4B (twice as much in HCT116 than in SW48)...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29724720/setd2-haploinsufficiency-for-microtubule-methylation-is-an-early-driver-of-genomic-instability-in-renal-cell-carcinoma
#4
Yun Chen Chiang, In Young Park, Esteban A Terzo, Durga Nand Tripathi, Frank M Mason, Catherine C Fahey, Menuka Karki, Charles B Shuster, Bo Hwa Sohn, Pratim Chowdhury, Reid T Powell, Ryoma Ohi, Yi-Hsuan Tsai, Aguirre A de Cubas, Abid Khan, Ian Davis, Brian D Strahl, Joel S Parker, Ruhee Dere, Cheryl Lyn Walker, W Kimryn Rathmell
Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (αTubK40me3) during mitosis, with αTubK40me3 required for genomic stability. We now show that mono-allelic, Setd2-deficient cells retaining H3K36me3 but not αTubK40me3 exhibit a dramatic increase in mitotic defects and micronuclei count with increased viability compared to bi-allelic loss...
May 3, 2018: Cancer Research
https://www.readbyqxmd.com/read/29716999/the-histone-methyltransferase-setd2-is-required-for-expression-of-acrosin-binding-protein-1and-protamines-and-essential-for-spermiogenesis-in-mice
#5
Xiaoli Zuo, Bowen Rong, Li Li, Ruitu Lv, Fei Lan, Ming-Han Tong
Spermatogenesis is precisely controlled by complex gene expression programs and involves epigenetic reprogramming including histone modification and DNA methylation. SET domain-containing 2 (Setd2) is the predominant histone methyltransferase catalyzing the trimethylation of histone H3 Lysine 36 (H3K36me3) and plays key roles in embryonic stem cell differentiation and somatic cell development. However, its role in male germ cell development remains elusive. Here we demonstrate an essential role of Setd2for spermiogenesis,the final stage of spermatogenesis...
May 1, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29706137/position-specific-intron-retention-is-mediated-by-the-histone-methyltransferase-sdg725
#6
Gang Wei, Kunpeng Liu, Ting Shen, Jinlei Shi, Bing Liu, Miao Han, Maolin Peng, Haihui Fu, Yifan Song, Jun Zhu, Aiwu Dong, Ting Ni
BACKGROUND: Intron retention (IR), the most prevalent alternative splicing form in plants, plays a critical role in gene expression during plant development and stress response. However, the molecular mechanisms underlying IR regulation remain largely unknown. RESULTS: Knockdown of SDG725, a histone H3 lysine 36 (H3K36)-specific methyltransferase in rice, leads to alterations of IR in more than 4700 genes. Surprisingly, IR events are globally increased at the 5' region but decreased at the 3' region of the gene body in the SDG725-knockdown mutant...
April 30, 2018: BMC Biology
https://www.readbyqxmd.com/read/29699903/evaluation-of-specific-modified-histones-in-lip-carcinogenesis
#7
Silas Antonio Juvencio de Freitas Filho, João Paulo Silva Servato, Rodrigo Tavares de Sá, Carla Silva Siqueira, Paulo Rogério de Faria, Adriano Mota Loyola, Sérgio Vitorino Cardoso
OBJECTIVE: Histones regulate chromatin density and therefore influence gene expression and cellular proliferation. These properties are modified by methylation, acetylation and phosphorylation of histones. The aim of this study was to investigate the variation of specific modified histones in actinic cheilitis (AC) and squamous cell carcinoma of the lip (SCCL). METHODS: Samples of non-neoplastic tissue of the lip (NNTL, n = 9), AC (n = 33), and SCCL (n = 27) were submitted to immunohistochemistry to detect the modified histones H3K36me3, H3K9ac, H4K12ac, and H3S10 ph...
April 22, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29682202/ctcf-kdm4a-complex-correlates-with-histone-modifications-that-negatively-regulate-chd5-gene-expression-in-cancer-cell-lines
#8
Lissania Guerra-Calderas, Rodrigo González-Barrios, Carlos César Patiño, Nicolás Alcaraz, Marisol Salgado-Albarrán, David Cantú de León, Clementina Castro Hernández, Yesennia Sánchez-Pérez, Héctor Aquiles Maldonado-Martínez, Inti A De la Rosa-Velazquez, Fernanda Vargas-Romero, Luis A Herrera, Alejandro García-Carrancá, Ernesto Soto-Reyes
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5 , and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29666467/ascorbic-acid-induces-global-epigenetic-reprogramming-to-promote-meiotic-maturation-and-developmental-competence-of-porcine-oocytes
#9
Xiao-Xia Yu, Yun-Hua Liu, Xiao-Man Liu, Pei-Chao Wang, Shuai Liu, Jia-Kun Miao, Zhi-Qiang Du, Cai-Xia Yang
L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 μM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29610279/h3k36me3-mediated-mismatch-repair-preferentially-protects-actively-transcribed-genes-from-mutation
#10
Yaping Huang, Liya Gu, Guo-Min Li
Histone H3 trimethylation at lysine 36 (H3K36me3) is an important histone mark involved in both transcription elongation and DNA mismatch repair (MMR). It is known that H3K36me3 recruits the mismatch-recognition protein MutSα to replicating chromatin via its physical interaction with MutSα's PWWP domain, but the exact role of H3K36me3 in transcription is undefined. Using chromatin immunoprecipitation combined with whole genome  DNA sequencing analysis, we demonstrate here that H3K36me3, together with MutSα, is involved in protecting against mutation, preferentially in actively transcribed genomic regions...
April 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29581865/luminal-breast-cancer-specific-circular-rnas-uncovered-by-a-novel-tool-for-data-analysis
#11
Lucia Coscujuela Tarrero, Giulio Ferrero, Valentina Miano, Carlo De Intinis, Laura Ricci, Maddalena Arigoni, Federica Riccardo, Laura Annaratone, Isabella Castellano, Raffaele A Calogero, Marco Beccuti, Francesca Cordero, Michele De Bortoli
Circular RNAs are highly stable molecules present in all eukaryotes generated by distinct transcript processing. We have exploited poly(A-) RNA-Seq data generated in our lab in MCF-7 breast cancer cells to define a compilation of exonic circRNAs more comprehensive than previously existing lists. Development of a novel computational tool, named CircHunter , allowed us to more accurately characterize circRNAs and to quantitatively evaluate their expression in publicly available RNA-Seq data from breast cancer cell lines and tumor tissues...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29535803/circulating-cell-free-nucleosomes-as-biomarkers-for-early-detection-of-colorectal-cancer
#12
Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29517958/atxr2-as-a-core-regulator-of-de-novo-root-organogenesis
#13
Kyounghee Lee, Ok-Sun Park, Pil Joon Seo
Tissue identity is plastically regulated in plants, and chromatin modifiers/remodelers are main players of cell fate changes. Callus formation is an intriguing example of cell fate transition. Leaf explants can form callus tissues, which resemble lateral root primordium, on callus-inducing medium (CIM). We recently demonstrated that the ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2) protein, which deposits H3K36me3 at genomic level, regulates callus formation on CIM. Consistent with the role of ATXR2 in conferring root identity, lateral root formation was significantly reduced in atxr2-deficient mutants...
March 4, 2018: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29514099/muscle-specific-histone-h3k36-dimethyltransferase-set-18-shortens-lifespan-of-caenorhabditis-elegans-by-repressing-daf-16a-expression
#14
Liangping Su, Hongyuan Li, Cheng Huang, Tingting Zhao, Yongjun Zhang, Xueqing Ba, Zhongwei Li, Yu Zhang, Baiqu Huang, Jun Lu, Yanmei Zhao, Xiaoxue Li
Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway...
March 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29499398/epigenetic-alteration-of-mismatch-repair-genes-in-the-population-chronically-exposed-to-arsenic-in-west-bengal-india
#15
Pritha Bhattacharjee, Tamalika Sanyal, Sandip Bhattacharjee, Pritha Bhattacharjee
INTRODUCTION: Arsenic exposure and its adverse health outcome, including the association with cancer risk are well established from several studies across the globe. The present study aims to analyze the epigenetic regulation of key mismatch repair (MMR) genes in the arsenic-exposed population. METHOD: A case-control study was conducted involving two hundred twenty four (N=224) arsenic exposed [with skin lesion (WSL=110) and without skin lesion (WOSL=114)] and one hundred and two (N=102) unexposed individuals...
May 2018: Environmental Research
https://www.readbyqxmd.com/read/29486199/loss-of-chromatin-remodeling-proteins-and-or-cdkn2a-associates-with-metastasis-of-pancreatic-neuroendocrine-tumors-and-reduced-patient-survival-times
#16
Somak Roy, William A LaFramboise, Ta-Chiang Liu, Dengfeng Cao, Alyssa Luvison, Caitlyn Miller, Maureen A Lyons, Roderick J O'Sullivan, Amer H Zureikat, Melissa E Hogg, Allan Tsung, Kenneth K Lee, Nathan Bahary, Randall E Brand, Jennifer S Chennat, Kenneth E Fasanella, Kevin McGrath, Marina N Nikiforova, Georgios I Papachristou, Adam Slivka, Herbert J Zeh, Aatur D Singhi
Despite prognostic grading and staging systems, it is a challenge to predict outcomes for patients with pancreatic neuroendocrine tumors (PanNETs). Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and alpha-thalassemia/mental retardation X-linked chromatin remodeler (ATRX). In tumors, mutations in DAXX or ATRX and corresponding loss of protein expression correlate with shorter times of disease-free survival and disease-specific survival of patients. However, DAXX or ATRX proteins were lost in only 50% of distant metastases analyzed...
March 2, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29478809/prdm9-methyltransferase-activity-is-essential-for-meiotic-dna-double-strand-break-formation-at-its-binding-sites
#17
Boubou Diagouraga, Julie A J Clément, Laurent Duret, Jan Kadlec, Bernard de Massy, Frédéric Baudat
The programmed formation of hundreds of DNA double-strand breaks (DSBs) is essential for proper meiosis and fertility. In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA-binding specificity of its zinc-finger domain. PRDM9 also has methyltransferase activity. Here, we show that this activity is required for H3K4me3 and H3K36me3 deposition and for DSB formation at PRDM9-binding sites. By analyzing mice that express two PRDM9 variants with distinct DNA-binding specificities, we show that each variant generates its own set of H3K4me3 marks independently from the other variant...
March 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29423916/epiproteome-profiling-of-cadmium-transformed-human-bronchial-epithelial-cells-by-quantitative-histone-post-translational-modification-enzyme-linked-immunosorbent-assay
#18
Zhan-Ling Liang, Dan-Dan Wu, Yue Yao, Fei-Yuan Yu, Lei Yang, Heng Wee Tan, Machteld N Hylkema, Marianne G Rots, Yan-Ming Xu, Andy T Y Lau
Cadmium (Cd), a carcinogenic toxic metal, is pervasively distributed in the soil, water and air. Chronic exposure to Cd has been correlated to lung disease development including cancers. Although many studies have been conducted to investigate the proteome response of cells challenged with Cd, the epiproteomic responses (i.e., global histone post-translational modifications [PTMs]), particularly in human lung cells, are largely unexplored. Here, we provide an epiproteome profiling of human bronchial epithelial cells (BEAS-2B) chronically treated with cadmium chloride (CdCl2 ), with the aim of identifying global epiproteomic signatures in response to Cd epigenotoxicity...
June 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29372509/early-flowering-in-short-days-efs-regulates-the-seed-size-in-arabidopsis
#19
Lingling Cheng, Sarfraz Shafiq, Wei Xu, Qianwen Sun
Post-transcriptional modifications, including histone modifications and DNA methylation, alter the chromatin landscape to regulate gene expression, thus control various cellular processes in plants. EARLY FLOWERING IN SHORT DAYS (EFS) is the major contributor for H3K36 methylation in Arabidopsis and is important for plant development. Here, we find that EFS is expressed in different stages of embryo morphogenesis, and the efs mutant produces larger embryo that results in enlarged seeds. Further analysis reveals that an imprinted gene MOP9...
February 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29351989/iterative-random-forests-to-discover-predictive-and-stable-high-order-interactions
#20
Sumanta Basu, Karl Kumbier, James B Brown, Bin Yu
Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order interactions drive gene expression presents a substantial statistical challenge. Building on random forests (RFs) and random intersection trees (RITs) and through extensive, biologically inspired simulations, we developed the iterative random forest algorithm (iRF)...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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