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T-ALL epigenetics

B-H Bin, S-H Lee, J Bhin, T Irié, S Kim, J Seo, K Mishima, T R Lee, D Hwang, T Fukada, E-G Cho
BACKGROUND: The skin is the first organ that manifests changes in response to zinc deficiency. However, the molecular mechanism underlying how zinc is involved in skin homeostasis, especially in its epigenetic regulation, is largely unknown. OBJECTIVES: In this study, we demonstrate the importance of zinc levels and the zinc transporter ZIP10 in the epigenetic maintenance of human epidermal homeostasis. METHODS: Adult human skin, including skin appendages were stained with anti-ZIP10 antibody...
October 19, 2018: British Journal of Dermatology
Elizabeth M Curtis, Nevena Krstic, Eloïse Cook, Stefania D'Angelo, Sarah R Crozier, Rebecca J Moon, Robert Murray, Emma Garratt, Paula Costello, Jane Cleal, Brogan Ashley, Nicholas J Bishop, Stephen Kennedy, Aris T Papageorghiou, Inez Schoenmakers, Robert Fraser, Saurabh V Gandhi, Ann Prentice, M Kassim Javaid, Hazel M Inskip, Keith M Godfrey, Christopher G Bell, Karen A Lillycrop, Cyrus Cooper, Nicholas C Harvey
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial of 1000IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery...
October 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
K Cui, B Wang, T Ma, B W Si, N F Zhang, Y Tu, Q Y Diao
The present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d...
October 12, 2018: Scientific Reports
Stella Aslibekyan, Laura Almasy, Michael A Province, Devin M Absher, Donna K Arnett
GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families ( N  = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study ( identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates...
2018: BMC Proceedings
Aldi T Kraja, Ping An, Petra Lenzini, Shiou J Lin, Christine Williams, James E Hicks, E Warwick Daw, Michael A Province
The GAW20 simulation data set is based upon the companion Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set that forms the real data example for GAW20. The simulated data problem consists of 200 simulated replications of what might happen if we were to repeat the GOLDN clinical trial 200 independent times, for these exact same subjects, but using a new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect on triglyceride response...
2018: BMC Proceedings
Paras Garg, Ricky S Joshi, Corey Watson, Andrew J Sharp
While population studies have resulted in detailed maps of genetic variation in humans, to date there are few robust maps of epigenetic variation. We identified sites containing clusters of CpGs with high inter-individual epigenetic variation, termed Variably Methylated Regions (VMRs) in five purified cell types. We observed that VMRs occur preferentially at enhancers and 3' UTRs. While the majority of VMRs have high heritability, a subset of VMRs within the genome show highly correlated variation in trans, forming co-regulated networks that have low heritability, differ between cell types and are enriched for specific transcription factor binding sites and biological pathways of functional relevance to each tissue...
October 2018: PLoS Genetics
M C Ovejero-Benito, A Reolid, P Sánchez-Jiménez, M Saiz-Rodríguez, E Muñoz-Aceituno, M Llamas-Velasco, S Martín-Vilchez, T Cabaleiro, M Román, D Ochoa, E Daudén, F Abad-Santos
INTRODUCTION: Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies. OBJECTIVE: To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab)...
September 27, 2018: Experimental Dermatology
J M Whitaker, A B Welsh, D W Hondorp, J C Boase, G T Merovich, S Welsh, C C Krueger
Lake sturgeon Acipenser fulvescens populations show a variety of movement patterns that are poorly understood. To compare two migratory phenotypes of A. fulvescens in the St. Clair River, MI, USA, multiple data types were analysed. Individual fish were classified into migratory phenotypes based on acoustic telemetry data collected 2012-2015. Acipenser fulvescens consistently showed movement from the St. Clair River upriver into Lake Huron or downriver into Lake St. Clair. The two migratory phenotypes were then compared for differences in morphometrics, genetics and epigenetics...
September 23, 2018: Journal of Fish Biology
A S Attermann, A M Bjerregaard, S K Saini, K Grønbæk, S R Hadrup
Human endogenous retroviruses (HERVs) have recently caught increased attention as a potential internal trigger to sensitize tumor cells to immunotherapies. HERVs are remnants of retroviral germline infections that resulted in chromosomal integration into all the cells of the progeny. Today, HERVs constitute ∼8% of the human genome, but most elements are highly degenerated, under strict epigenetic regulation, and rarely expressed in healthy tissues. However, cancer cells are specifically prone to reactivate the expression of HERV elements due to epigenetic dysregulation that accumulate during malignant transformation and when using epigenetic therapies...
September 18, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Difeng Fang, Kairong Cui, Kairui Mao, Gangqing Hu, Rao Li, Mingzhu Zheng, Nicolas Riteau, Steven L Reiner, Alan Sher, Keji Zhao, Jinfang Zhu
T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine IL-21. Mature Tfh cells are also capable of producing IFN-γ without expressing the Th1 transcription factor T-bet. Whether this IFN-γ-producing Tfh population represents a unique Tfh subset with a distinct differentiation pathway is poorly understood. By using T-bet fate-mapping mouse strains, we discovered that almost all the IFN-γ-producing Tfh cells have previously expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity analysis indicated that the Ifng gene locus is partially accessible in this "ex-T-bet" population with a history of T-bet expression...
September 19, 2018: Journal of Experimental Medicine
Alex Shimura Yamashita, Marina da Costa Rosa, Alexandra Borodovsky, William T Festuccia, Timothy Chan, Gregory J Riggins
Background: Isocitrate Deyhydrogenase (IDH) mutant gliomas are comprised of the majority of grade II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produces D-2-hydroxyglutarate (2HG). 2-HG interferes with cell reactions using alpha ketoglutarate leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis. Methods: Human IDH1 WT and IDH1R132H cell lines and patient derived xenografts (PDX) were used to evaluate the FDA-approved DNA demethylating agent 5-Azacytidine (5-Aza)...
September 3, 2018: Neuro-oncology
Niedziela Agnieszka
Abiotic stressors such as drought, salinity, and exposure to heavy metals can induce epigenetic changes in plants. In this study, liquid chromatography (RP-HPLC), methylation amplified fragment length polymorphisms (metAFLP), and methylation-sensitive amplification polymorphisms (MSAP) analysis was used to investigate the effects of aluminum (Al) stress on DNA methylation levels in the crop species triticale. RP-HPLC, but not metAFLP or MSAP, revealed significant differences in methylation between Al-tolerant (T) and non-tolerant (NT) triticale lines...
November 2018: Journal of Applied Genetics
J T Paiva, M D V De Resende, R T Resende, H R Oliveira, H T Silva, G C Caetano, A A Calderano, P S Lopes, J M S Viana, F F Silva
1. The aim of the following experiment was to estimate transgenerational epigenetic variance for egg quality traits using genealogical and phenotypic information in meat-type quail. Measured traits included egg length (EL) and width (EWD), albumen weight (AW), shell weight (SW), yolk weight (YW) and egg weight (EW). 2. A total of 391 birds were evaluated for egg quality by collecting a sample of one egg per bird, during three consecutive days, starting on the 14th d of production. Analyses were performed using mixed models including the random epigenetic effect...
September 21, 2018: British Poultry Science
Sangkyu Kim, Jennifer Wyckoff, Anne-T Morris, Annemarie Succop, Ally Avery, Glen E Duncan, S Michal Jazwinski
Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites...
August 22, 2018: GeroScience
Eric D Bankaitis, Andrew Ha, Calvin J Kuo, Scott T Magness
Renewal of the intestinal epithelium occurs approximately every week and requires a careful balance between cell proliferation and differentiation to maintain proper lineage ratios and support absorptive, secretory, and barrier functions. We review models used to study the mechanisms by which intestinal stem cells (ISCs) fuel the rapid turnover of the epithelium during homeostasis and might support epithelial regeneration after injury. In anatomically defined zones of the crypt stem cell niche, phenotypically distinct active and reserve ISC populations are believed to support homeostatic epithelial renewal and injury-induced regeneration, respectively...
August 15, 2018: Gastroenterology
Valerie Lee, Judy S Wang, Marianna L Zahurak, Elske C Gootjes, Henk M W Verheul, Rose M Parkinson, Zachary Kerner, Anup Sharma, Gary L Rosner, Ana De Jesus-Acosta, Daniel A Laheru, Dung T Le, Aram Oganesian, Ellen Lilly-Foreman, Thomas Brown, Peter A Jones, Stephen B Baylin, Nita Ahuja, Nilofer A Azad
PURPOSE: Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of resistance with administration of hypomethylating agents. We evaluated the safety and tolerability of guadecitabine and irinotecan in mCRC patients previously treated with irinotecan. EXPERIMENTAL DESIGN: In this 3+3 dose-escalation study, mCRC patients previously exposed to irinotecan received guadecitabine days 1-5 of a 28 day cycle and irinotecan 125mg/m2 days 8 and 15 [dose level (DL) 1, guadecitabine 45mg/m2; DL -1: guadecitabine 30mg/m2; DL -1G: guadecitabine 30mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45mg/m2 with GFS...
August 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Marie-Pierre Belot, Anne-Laure Castell, Sophie Le Fur, Pierre Bougnères
IL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+ T cells in response to various stimuli and is constitutive in regulatory T cells (Tregs). We selected for our study 18 CpGs located within cognate regulatory regions of the IL2RA locus and characterized their methylation in naive, regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502) show dynamic, active demethylation during the in vitro activation of naive CD4+ T cells...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Przemyslaw Szafranski, Ewelina Kośmider, Qian Liu, Justyna A Karolak, Lauren Currie, Sandhya Parkash, Stephen G Kahler, Elizabeth Roeder, Rebecca O Littlejohn, Thomas S DeNapoli, Felix R Shardonofsky, Cody Henderson, George Powers, Virginie Poisson, Denis Bérubé, Luc Oligny, Jacques L Michaud, Sandra Janssens, Kris De Coen, Jo Van Dorpe, Annelies Dheedene, Matthew T Harting, Matthew D Weaver, Amir M Khan, Nina Tatevian, Jennifer Wambach, Kathleen A Gibbs, Edwina Popek, Anna Gambin, Paweł Stankiewicz
Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements...
August 6, 2018: Human Mutation
Changshan Wang, Motohiko Oshima, Daisuke Sato, Hirotaka Matsui, Sho Kubota, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Shuhei Koide, Jun Matsubayashi, Makiko Mochizuki-Kashio, Takako Nakano-Yokomizo, Jie Bai, Toshitaka Nagao, Akinori Kanai, Atsushi Iwama, Goro Sashida
Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs...
August 31, 2018: Journal of Clinical Investigation
David Bending, Masahiro Ono
Studies on regulatory T cells (Treg) have focused on thymic Treg as a stable lineage of immunosuppressive T cells, the differentiation of which is controlled by the transcription factor Foxp3. This lineage perspective, however, may constrain hypotheses regarding the role of Foxp3 and Treg in vivo, particularly in clinical settings and immunotherapy development. In this review, we synthesise a new perspective on the role of Foxp3 as a dynamically expressed gene, and thereby revisit the molecular mechanisms for the transcriptional regulation of Foxp3...
August 4, 2018: Clinical and Experimental Immunology
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