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https://www.readbyqxmd.com/read/29133398/analysis-of-high-resolution-3d-intrachromosomal-interactions-aided-by-bayesian-network-modeling
#1
Xizhe Zhang, Sergio Branciamore, Grigoriy Gogoshin, Andrei S Rodin, Arthur D Riggs
Long-range intrachromosomal interactions play an important role in 3D chromosome structure and function, but our understanding of how various factors contribute to the strength of these interactions remains poor. In this study we used a recently developed analysis framework for Bayesian network (BN) modeling to analyze publicly available datasets for intrachromosomal interactions. We investigated how 106 variables affect the pairwise interactions of over 10 million 5-kb DNA segments in the B-lymphocyte cell line GB12878...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#2
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29097680/epigenome-wide-association-studies-identify-dna-methylation-associated-with-kidney-function
#3
Audrey Y Chu, Adrienne Tin, Pascal Schlosser, Yi-An Ko, Chengxiang Qiu, Chen Yao, Roby Joehanes, Morgan E Grams, Liming Liang, Caroline A Gluck, Chunyu Liu, Josef Coresh, Shih-Jen Hwang, Daniel Levy, Eric Boerwinkle, James S Pankow, Qiong Yang, Myriam Fornage, Caroline S Fox, Katalin Susztak, Anna Köttgen
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28982592/human-amyloid-%C3%AE-peptide-and-tau-co-expression-impairs-behavior-and-causes-specific-gene-expression-changes-in-caenorhabditis-elegans
#4
Chenyin Wang, Valeria Saar, Ka Lai Leung, Liang Chen, Garry Wong
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-β peptide (Aβ) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing Aβ1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans...
October 2, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28978690/aryl-hydrocarbon-receptor-activation-suppresses-ebf1-and-pax5-and-impairs-human-b-lymphopoiesis
#5
Jinpeng Li, Sudin Bhattacharya, Jiajun Zhou, Ashwini S Phadnis-Moghe, Robert B Crawford, Norbert E Kaminski
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates biological responses to endogenous and environmental chemical cues. Increasing evidence shows that the AHR plays physiological roles in regulating development, homeostasis, and function of a variety of cell lineages in the immune system. However, the role of AHR in human B cell development has not been investigated. Toward this end, an in vitro feeder-free human B cell developmental model system was employed using human cord blood CD34(+) hematopoietic stem/progenitor cells...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28977418/developmentally-regulated-higher-order-chromatin-interactions-orchestrate-b-cell-fate-commitment
#6
Ravi Boya, Anurupa Devi Yadavalli, Sameena Nikhat, Sreenivasulu Kurukuti, Dasaradhi Palakodeti, Jagan M R Pongubala
Genome organization in 3D nuclear-space is important for regulation of gene expression. However, the alterations of chromatin architecture that impinge on the B cell-fate choice of multi-potent progenitors are still unclear. By integrating in situ Hi-C analyses with epigenetic landscapes and genome-wide expression profiles, we tracked the changes in genome architecture as the cells transit from a progenitor to a committed state. We identified the genomic loci that undergo developmental switch between A and B compartments during B-cell fate determination...
August 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28968461/ebf1-binds-to-ebna2-and-promotes-the-assembly-of-ebna2-chromatin-complexes-in-b-cells
#7
Laura V Glaser, Simone Rieger, Sybille Thumann, Sophie Beer, Cornelia Kuklik-Roos, Dietmar E Martin, Kerstin C Maier, Marie L Harth-Hertle, Björn Grüning, Rolf Backofen, Stefan Krebs, Helmut Blum, Ralf Zimmer, Florian Erhard, Bettina Kempkes
Epstein-Barr virus (EBV) infection converts resting human B cells into permanently proliferating lymphoblastoid cell lines (LCLs). The Epstein-Barr virus nuclear antigen 2 (EBNA2) plays a key role in this process. It preferentially binds to B cell enhancers and establishes a specific viral and cellular gene expression program in LCLs. The cellular DNA binding factor CBF1/CSL serves as a sequence specific chromatin anchor for EBNA2. The ubiquitous expression of this highly conserved protein raises the question whether additional cellular factors might determine EBNA2 chromatin binding selectively in B cells...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#8
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28886309/the-correlation-between-pax5-deletion-and-patients-survival-in-iranian-children-with-precursor-b-cell-acute-lymphocytic-leukemia
#9
A Moafi, A Zojaji, R Salehi, S Najafi Dorcheh, S Rahgozar
Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012...
August 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28877031/genetic-associations-with-gestational-duration-and-spontaneous-preterm-birth
#10
Ge Zhang, Bjarke Feenstra, Jonas Bacelis, Xueping Liu, Lisa M Muglia, Julius Juodakis, Daniel E Miller, Nadia Litterman, Pan-Pan Jiang, Laura Russell, David A Hinds, Youna Hu, Matthew T Weirauch, Xiaoting Chen, Arun R Chavan, Günter P Wagner, Mihaela Pavličev, Mauris C Nnamani, Jamie Maziarz, Minna K Karjalainen, Mika Rämet, Verena Sengpiel, Frank Geller, Heather A Boyd, Aarno Palotie, Allison Momany, Bruce Bedell, Kelli K Ryckman, Johanna M Huusko, Carmy R Forney, Leah C Kottyan, Mikko Hallman, Kari Teramo, Ellen A Nohr, George Davey Smith, Mads Melbye, Bo Jacobsson, Louis J Muglia
BACKGROUND: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28860953/comparative-analyses-of-signature-genes-in-acute-rejection-and-operational-tolerance
#11
Jeong-Woo Choi, Yong-Hee Kim, Ji Won Oh
Using biomarkers as prediction tools or therapeutic targets can be a valuable strategy in transplantation. Recent studies identified biomarkers of acute rejection (AR) and operational tolerance (TOL) through the application of meta-analysis. In this study, we comparatively analyzed the signature genes in acute rejection and operational tolerance seen in human allogeneic transplantations using massive bioinformatical meta-analysis. To identify the signature genes in opposite immunological conditions, AR and TOL, we first collected the 1,252 gene expression data specifically intended for those circumstances...
August 2017: Immune Network
https://www.readbyqxmd.com/read/28794029/coordinate-regulation-of-tet2-and-ebna2-control-dna-methylation-state-of-latent-epstein-barr-virus
#12
Fang Lu, Andreas Wiedmer, Kayla A Martin, Priyankara J M S Wickramasinghe, Andrew V Kossenkov, Paul M Lieberman
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28771871/predicting-nk-cell-subsets-using-gene-expression-levels-in-peripheral-blood-and-endometrial-biopsy-specimens
#13
Michael L Davies, Svetlana V Dambaeva, Dimantha Katukurundage, Miroslava Repak, Alice Gilman-Sachs, Joanne Kwak-Kim, Kenneth D Beaman
PROBLEM: In molecular analysis of tissue biopsy specimens, one crucial aspect is characterization of immune cell populations. This is especially important for evaluation of uterine receptivity by assessing levels of lymphocyte populations including CD56(bright) CD16- uterine NK cells and CD56(dim) CD16+ conventional NK cells. Our objective was to investigate whether measuring total RNA transcripts from a tissue specimen would accurately reflect immune cell levels and be a new technique to assess immune cell subsets...
August 3, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28736168/light-dependent-degradation-of-pif3-by-scf-ebf1-2-promotes-a-photomorphogenic-response-in-arabidopsis
#14
Jie Dong, Weimin Ni, Renbo Yu, Xing Wang Deng, Haodong Chen, Ning Wei
Plant seedlings emerging from darkness into the light environment undergo photomorphogenesis, which enables autotrophic growth with optimized morphology and physiology. During this transition, plants must rapidly remove photomorphogenic repressors accumulated in the dark. Among them is PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor promoting hypocotyl growth. Here we report that, in response to light activation of phytochrome photoreceptors, EIN3-BINDING F BOX PROTEINs (EBFs) 1 and 2 mediate PIF3 protein degradation in a manner dependent on light-induced phosphorylation of PIF3...
August 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#15
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28692033/spontaneous-loss-of-b-lineage-transcription-factors-leads-to-pre-b-leukemia-in-ebf1-bcl-xl-tg-mice
#16
J A Ramírez-Komo, M A Delaney, D Straign, K Lukin, M Tsang, B M Iritani, J Hagman
Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1(+/-)Bcl-xL(Tg) mice, which express the anti-apoptotic factor Bcl-xL in B cells...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28655536/b-cell-identity-as-a-metabolic-barrier-against-malignant-transformation
#17
REVIEW
Lai N Chan, Markus Müschen
B-lineage and myeloid leukemia cells are often transformed by the same oncogenes, but have different biological and clinical characteristics. Although B-lineage acute lymphoblastic leukemia (B-ALL) cells are characterized by a state of chronic energy deficit, myeloid leukemia cells show abundant energy reserve. Interestingly, fasting has been demonstrated to inhibit selectively the development of B-ALL but not myeloid leukemia, further suggesting that lineage identity may be linked to divergent metabolic states in hematopoietic malignancies...
September 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28631637/an-integrated-genomic-profile-that-includes-copy-number-alterations-is-highly-predictive-of-minimal-residual-disease-status-in-childhood-precursor-b-lineage-acute-lymphoblastic-leukemia
#18
Nikhil Patkar, P G Subramanian, Prashant Tembhare, Sneha Mandalia, Gaurav Chaterjee, Nikhil Rabade, Rohan Kodgule, Karishma Chopra, Asma Bibi, Swapnali Joshi, Shruti Chaudhary, Russel Mascerhenas, Pratibha Kadam-Amare, Gaurav Narula, Brijesh Arora, Shripad Banavali, Sumeet Gujral
INTRODUCTION: Copy number alterations (CNA) have been described in childhood precursor B-lineage acute lymphoblastic leukemia (B-ALL) which in conjunction with chromosomal abnormalities drive leukemogenesis. There is no consensus on the clinical incorporation of CNA in B-ALL. An integrated genomic classification (IGC) has been proposed which includes CNA and cytogenetics. METHODS: We correlated this IGC with immunophenotypic minimal residual disease (MRD) as well as other standard criteria for 245 patients of B-ALL such as National Cancer Institute (NCI) risk, D+8 prednisolone response, cytogenetics, and ploidy status...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28630421/a-genome-wide-association-study-of-anorexia-nervosa-suggests-a-risk-locus-implicated-in-dysregulated-leptin-signaling
#19
Dong Li, Xiao Chang, John J Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J Bhoj, Nora Robinson, Debra Abrams, Yun R Li, Jonathan P Bradfield, Cecilia E Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Yiran Guo, Haijun Qiu, Frank D Mentch, Kelly A Thomas, Rosetta M Chiavacci, Roger Cone, Bingshan Li, Patrick A Sleiman, Hakon Hakonarson
We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#20
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
October 2017: Genes, Chromosomes & Cancer
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