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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
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 8, 2018: Plant Signaling & Behavior
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
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...
February 27, 2018: Environmental Research
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 ATRX 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...
February 24, 2018: Gastroenterology
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...
February 14, 2018: Molecular Cell
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...
February 9, 2018: Journal of Applied Toxicology: JAT
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...
January 9, 2018: Science China. Life Sciences
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)...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jean-Louis Guéant, Céline Chéry, Abderrahim Oussalah, Javad Nadaf, David Coelho, Thomas Josse, Justine Flayac, Aurélie Robert, Isabelle Koscinski, Isabelle Gastin, Pierre Filhine-Tresarrieu, Mihaela Pupavac, Alison Brebner, David Watkins, Tomi Pastinen, Alexandre Montpetit, Fadi Hariri, David Tregouët, Benjamin A Raby, Wendy K Chung, Pierre-Emmanuel Morange, D Sean Froese, Matthias R Baumgartner, Jean-François Benoist, Can Ficicioglu, Virginie Marchand, Yuri Motorin, Chrystèle Bonnemains, François Feillet, Jacek Majewski, David S Rosenblatt
To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name "epi-cblC". The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation...
January 4, 2018: Nature Communications
J Bu, A Chen, X Yan, F He, Y Dong, Y Zhou, J He, D Zhan, P Lin, Y Hayashi, Y Sun, Y Zhang, Z Xiao, H L Grimes, Q F Wang, G Huang
Previously, we identified SETD2 loss-of-function mutations in 22% of MLL-rearranged (MLLr) acute leukemia patients, implicating a mechanism for cooperativity between SETD2 mutations and MLL fusions. However, the detailed mechanism of how SETD2-H3K36me3 downregulation accelerates MLLr leukemia remains unclear. Here, we show that in MLLr leukemia, both H3K79me2 and H3K36me3 are aberrantly elevated and co-enriched in a group of genes. SETD2 inactivation leads to a global reduction of H3K36me3 and a further elevation of H3K79me2, but does not change the expression of known MLL fusion target genes...
November 29, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tao Lin, Reza K Oqani, Jae Eun Lee, Jeong Won Kang, So Yeon Kim, Eun Seok Cho, Yong Dae Jeong, Jun Jong Baek, Dong Il Jin
In this study, we used a pig model to investigate the effects of α-solanine (a natural toxin found mainly in potato sprouts) on oocyte maturation, quality and subsequent embryonic development. We found that α-solanine (10 μM) disturbed meiotic resumption and increased abnormal spindle formation and altered the cortical granule (CG) distribution compared with the untreated group. α-Solanine triggered autophagy and apoptosis by increasing the expressions of autophagy-related genes (LC3, ATG7, and LAMP2) and apoptotic related genes (BAX and CASP3)...
December 13, 2017: Reproductive Toxicology
Kyster K Nanan, Cody Ocheltree, David Sturgill, Mariana D Mandler, Maria Prigge, Garima Varma, Shalini Oberdoerffer
Actively transcribed genes adopt a unique chromatin environment with characteristic patterns of enrichment. Within gene bodies, H3K36me3 and cytosine DNA methylation are elevated at exons of spliced genes and have been implicated in the regulation of pre-mRNA splicing. H3K36me3 is further responsive to splicing, wherein splicing inhibition led to a redistribution and general reduction over gene bodies. In contrast, little is known of the mechanisms supporting elevated DNA methylation at actively spliced genic locations...
December 15, 2017: Nucleic Acids Research
Arko Sen, Katherine Gurdziel, Jenney Liu, Wen Qu, Oluwademi O Nuga, Rayanne B Burl, Maik Hüttemann, Roger Pique-Regi, Douglas M Ruden
Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. This may lead to cognitive dysfunction, depression and increased susceptibility to life threatening diseases, such as epilepsy and Alzheimer's disease. To investigate the underlying genetic and molecular basis of TBI, we subjected w 1118 Drosophila melanogaster to mild closed head trauma and found that mitochondrial activity is reduced in the brains of these flies 24 h after inflicting trauma. To determine the transcriptomic changes after mild TBI, we collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses...
2017: Frontiers in Genetics
Maolin Peng, Zepeng Li, Nana Zhou, Mengmeng Ma, Yupei Jiang, Aiwu Dong, Wen-Hui Shen, Lin Li
Shade avoidance syndrome (SAS) allows a plant grown in a densely populated environment to maximize opportunities to access to sunlight. Although it is well established that SAS is accompanied by gene expression changes, the underlying molecular mechanism needs to be elucidated. Here, we identify the H3K4me3/H3K36me3-binding proteins, Morf Related Gene (MRG) group proteins MRG1 and MRG2, as positive regulators of shade-induced hypocotyl elongation in Arabidopsis ( Arabidopsis thaliana ). MRG2 binds PHYTOCHROME-INTERACTING FACTOR7 (PIF7) and regulates the expression of several common downstream target genes, including YUCCA8 and IAA19 involved in the auxin biosynthesis or response pathway and PRE1 involved in brassinosteroid regulation of cell elongation...
February 2018: Plant Physiology
Kyounghee Lee, Ok-Sun Park, Pil Joon Seo
Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus tissues in vitro. Reversible cellular differentiation-dedifferentiation processes in higher eukaryotes are controlled mainly by chromatin modifications. We demonstrate that ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2), a histone lysine methyltransferase that promotes the accumulation of histone H3 proteins that are trimethylated on lysine 36 (H3K36me3) during callus formation, promotes early stages of cellular dedifferentiation through activation of LATERAL ORGAN BOUNDARIES DOMAIN ( LBD ) genes...
November 28, 2017: Science Signaling
Slavica Janevska, Leonie Baumann, Christian M K Sieber, Martin Münsterkötter, Jonas Ulrich, Jörg Kämper, Ulrich Güldener, Bettina Tudzynski
In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete Fusarium fujikuroi In Saccharomyces cerevisiae, one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus...
November 16, 2017: Genetics
Junfei Zhou, Fang Wang, Chang Xu, Zipeng Zhou, Wei Zhang
JMJD2A is a JmjC histone demethylase that catalyzes the demethylation of di- and trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). The role of spinal JMJD2A-dependent histone demethylation in nociception hypersensitivity development remains elusive. Here we reported that the JMJD2A responded to neuropathic pain and participated in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a were significantly increased in the neurons of mouse undergoing neuropathic pain induced by sciatic nerve chronic constrictive injury (CCI) or unilateral spared nerve injury (SNI)...
December 1, 2017: Experimental Cell Research
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...
December 1, 2017: Nucleic Acids Research
Brenton G Mar, S Haihua Chu, Josephine D Kahn, Andrei V Krivtsov, Richard Koche, Cecilia A Castellano, Jacob L Kotlier, Rebecca L Zon, Marie E McConkey, Jonathan Chabon, Ryan Chappell, Peter V Grauman, James J Hsieh, Scott A Armstrong, Benjamin L Ebert
Mutations in SETD2, encoding the histone 3 lysine 36 trimethyltransferase, are enriched in relapsed acute lymphoblastic leukemia and MLL-rearranged acute leukemia. We investigated the impact of SETD2 mutations on chemotherapy sensitivity in isogenic leukemia cell lines and in murine leukemia generated from a conditional knockout of Setd2. SETD2 mutations led to resistance to DNA-damaging agents, cytarabine, 6-thioguanine, doxorubicin, and etoposide, but not to a non-DNA damaging agent, l-asparaginase. H3K36me3 localizes components of the DNA damage response (DDR) pathway and SETD2 mutation impaired DDR, blunting apoptosis induced by cytotoxic chemotherapy...
December 14, 2017: Blood
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