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https://www.readbyqxmd.com/read/29242640/effects-of-maternal-obesity-on-wharton-s-jelly-mesenchymal-stromal-cells
#1
Heba Badraiq, Aleksandra Cvoro, Antonio Galleu, Marisa Simon, Cristian Miere, Carl Hobbs, Reiner Schulz, Richard Siow, Francesco Dazzi, Dusko Ilic
We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord's Wharton's Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients. In this pilot study on umbilical cords post partum from healthy non-obese (BMI = 19-25; n = 7) and obese (BMI ≥ 30; n = 7) donors undergoing elective Cesarean section, we found that WJ MSC from obese donors showed slower population doubling and a stronger immunosuppressive activity...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#2
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29233839/genetics-of-tumors-of-the-adrenal-cortex
#3
Fidéline Bonnet-Serrano, Jerome Bertherat
This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD) which can be sporadic or part of Carney complex, and primary bilateral macro nodular adrenal hyperplasia (PBMAH). The bilateral nature of tumors suggests the existence of an underlying genetic predisposition...
December 12, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29228658/dna-methylation-landscape-of-hepatoblastomas-reveals-arrest-at-early-stages-of-liver-differentiation-and-cancer-related-alterations
#4
Mariana Maschietto, Tatiane Cristina Rodrigues, André Yoshiaki Kashiwabara, Érica Sara Souza de Araujo, Talita Ferreira Marques Aguiar, Cecilia Maria Lima da Costa, Isabela Werneck da Cunha, Luciana Dos Reis Vasques, Monica Cypriano, Helena Brentani, Silvia Regina Caminada de Toledo, Peter Lees Pearson, Dirce Maria Carraro, Carla Rosenberg, Ana C V Krepischi
Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228040/consequences-of-supplying-methyl-donors-during-pregnancy-on-the-methylome-of-the-offspring-from-lactating-and-non-lactating-dairy-cattle
#5
Alex Bach, Anna Aris, Isabel Guasch
The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (non-lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to non-lactating and three to lactating dams) were blood-sampled to determine their full methylome...
2017: PloS One
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#6
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29224166/dna-methylation-analysis-from-blood-spots-increasing-yield-and-quality-for-genome-wide-and-locus-specific-methylation-analysis
#7
Akram Ghantous, Hector Hernandez-Vargas, Zdenko Herceg
Blood represents an easily accessible human tissue for numerous research and clinical applications, including surrogate roles for biomarkers of other tissues. Dried blood spots (DBS) are space- and cost-efficient storage forms of blood while stably retaining many of its chemical constituents. Consequently, neonatal DBS are routinely collected in many countries, and their biobanks represent gold mines for research. However, the utility of DBS is restricted by the limited amount and quality of extractable biomolecules (including DNA), especially for genome-wide profiling...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224149/nucleosome-occupancy-and-methylome-sequencing-nome-seq
#8
Fides D Lay, Theresa K Kelly, Peter A Jones
Various methodologies are available to interrogate specific components of epigenetic mechanisms such as DNA methylation or nucleosome occupancy at both the locus-specific and the genome-wide level. It has become increasingly clear, however, that comprehension of the functional interactions between epigenetic mechanisms is critical for understanding how cellular transcription programs are regulated or deregulated during normal and disease development. The Nucleosome Occupancy and Methylome sequencing (NOMe-seq) assay allows us to directly measure the relationship between DNA methylation and nucleosome occupancy by taking advantage of the methyltransferase M...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224147/comprehensive-whole-dna-methylome-analysis-by-integrating-medip-seq-and-mre-seq
#9
Xiaoyun Xing, Bo Zhang, Daofeng Li, Ting Wang
Understanding the role of DNA methylation often requires accurate assessment and comparison of these modifications in a genome-wide fashion. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA CpG methylomes. These include whole genome bisulfite sequencing (WGBS), Reduced-Representation Bisulfite-Sequencing (RRBS), and enrichment-based methods such as MeDIP-seq, MBD-seq, and MRE-seq. An investigator needs a method that is flexible with the quantity of input DNA, provides the appropriate balance among genomic CpG coverage, resolution, quantitative accuracy, and cost, and comes with robust bioinformatics software for analyzing the data...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224145/methyl-cpg-binding-domain-sequencing-mbd-seq
#10
Karolina A Aberg, Robin F Chan, Linying Xie, Andrey A Shabalin, Edwin J C G van den Oord
Detailed biological knowledge about the potential importance of the methylome is typically lacking for common diseases. Therefore, methylome-wide association studies (MWAS) are critical to detect disease relevant methylation sites. Methyl-CpG-binding domain sequencing (MBD-seq) offers potential advantages compared to antibody-based enrichment, but performance depends critically on using an optimal protocol. Using an optimized protocol, MBD-seq can approximate the sensitivity/specificity obtained with whole-genome bisulfite sequencing, but at a fraction of the costs and time to complete the project...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224142/post-bisulfite-adaptor-tagging-for-pcr-free-whole-genome-bisulfite-sequencing
#11
Fumihito Miura, Takashi Ito
Post-bisulfite adaptor tagging (PBAT) is a highly efficient procedure to construct libraries for whole-genome bisulfite sequencing (WGBS). PBAT attaches adaptors to bisulfite-converted genomic DNA to circumvent bisulfite-induced degradation of library DNA inherent to conventional WGBS protocols. Consequently, it enables PCR-free WGBS from nanogram quantities of mammalian DNA, thereby serving as an invaluable tool for methylomics.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224141/tagmentation-based-library-preparation-for-low-dna-input-whole-genome-bisulfite-sequencing
#12
Dieter Weichenhan, Qi Wang, Andrew Adey, Stephan Wolf, Jay Shendure, Roland Eils, Christoph Plass
Aberrations of the DNA methylome contribute to onset and progression of diseases. Whole genome bisulfite sequencing (WGBS) is the only analytical method covering the complete methylome. Alternative methods requiring less DNA than WGBS analyze only a minor portion of the methylome and do not cover important regulatory features like enhancers and noncoding RNAs. In tagmentation-based WGBS (TWGBS), several DNA and time-consuming steps of the conventional WGBS library preparation are circumvented by the use of a hyperactive transposase, which simultaneously fragments DNA and appends sequencing adapters...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222412/ancestral-perinatal-obesogen-exposure-results-in-a-transgenerational-thrifty-phenotype-in-mice
#13
Raquel Chamorro-Garcia, Carlos Diaz-Castillo, Bassem M Shoucri, Heidi Käch, Ron Leavitt, Toshi Shioda, Bruce Blumberg
Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants. This transgenerational inheritance has significant implications for understanding disease etiology. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the F4 obesity is consistent with a leptin resistant, thrifty phenotype...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221486/a-screening-system-to-identify-transcription-factors-that-induce-binding-site-directed-dna-demethylation
#14
Takahiro Suzuki, Shiori Maeda, Erina Furuhata, Yuri Shimizu, Hajime Nishimura, Mami Kishima, Harukazu Suzuki
BACKGROUND: DNA methylation is a fundamental epigenetic modification that is involved in many biological systems such as differentiation and disease. We and others recently showed that some transcription factors (TFs) are involved in the site-specific determination of DNA demethylation in a binding site-directed manner, although the reports of such TFs are limited. RESULTS: Here, we develop a screening system to identify TFs that induce binding site-directed DNA methylation changes...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29220649/loud-and-clear-epitranscriptomic-m1a-signals-now-in-single-base-resolution
#15
Dan Dominissini, Gideon Rechavi
In this issue of Molecular Cell, Li et al. (2017) map N1-methyladenosine (m1A) with base precision, parsing the methylome into subsets differing in location, sequence-structure features, and catalyzing enzymes, thereby aiding functional investigation.
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29215068/integrated-dna-methylome-and-transcriptome-analysis-reveals-the-ethylene-induced-flowering-pathway-genes-in-pineapple
#16
Jiabin Wang, Zhiying Li, Ming Lei, Yunliu Fu, Jiaju Zhao, Mengfei Ao, Li Xu
Ethylene has long been used to promote flowering in pineapple production. Ethylene-induced flowering is dose dependent, with a critical threshold level of ethylene response factors needed to trigger flowering. The mechanism of ethylene-induced flowering is still unclear. Here, we integrated isoform sequencing (iso-seq), Illumina short-reads sequencing and whole-genome bisulfite sequencing (WGBS) to explore the early changes of transcriptomic and DNA methylation in pineapple following high-concentration ethylene (HE) and low-concentration ethylene (LE) treatment...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29210663/dna-methylation-a-frontier-in-tooth-organogenesis-and-developmental-dental-defects
#17
Liwei Zheng, Hongyu Li, Zhou Yachuan, Wei Du, Xin Xu, Ling Ye, Xuedong Zhou, Mian Wan
Tooth development relies on interactions between epithelial and mesenchymal tissues, which is controlled by sophisticated networks of conserved signaling. The signaling networks regulating odontogenesis have been well characterized, but the mechanisms underlying remain to be elucidated. Researches on mammals have revealed that the genomic methylation, which occurs on cytosine residues, regulates certain genes transcription. Consequently, DNA methylation plays a crucial role in spatiotemporal organization of signaling pathways, and is essential for organogenesis...
December 6, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29209432/epigenetic-modifications-of-the-vgf-gene-in-human-non-small-cell-lung-cancer-tissues-pave-the-way-towards-enhanced-expression
#18
Sebastian Marwitz, Lena Heinbockel, Swetlana Scheufele, Dörte Nitschkowski, Christian Kugler, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Hwang et al. recently showed that VGF substantially contributes to the resistance of human lung cancer cells towards epidermal growth factor receptor kinase inhibitors. This was further linked to enhanced epithelial-mesenchymal transition. Here, we demonstrate that VGF is epigenetically modified in non-small cell lung cancer tissues compared to corresponding tumor-free lung tissues from the same donors by using methylome bead chip analyses. These epigenetic modifications trigger an increased transcription of the VGF gene within the tumors, which then leads to an increased expression of the protein, facilitating epithelial-mesenchymal transition, and the resistance to kinase inhibitors...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29203909/dynamic-epigenomic-landscapes-during-early-lineage-specification-in-mouse-embryos
#19
Yu Zhang, Yunlong Xiang, Qiangzong Yin, Zhenhai Du, Xu Peng, Qiujun Wang, Miguel Fidalgo, Weikun Xia, Yuanyuan Li, Zhen-Ao Zhao, Wenhao Zhang, Jing Ma, Feng Xu, Jianlong Wang, Lei Li, Wei Xie
In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29203669/islet-cells-share-promoter-hypomethylation-independently-of-expression-but-exhibit-cell-type-specific-methylation-in-enhancers
#20
Daniel Neiman, Joshua Moss, Merav Hecht, Judith Magenheim, Sheina Piyanzin, A M James Shapiro, Eelco J P de Koning, Aharon Razin, Howard Cedar, Ruth Shemer, Yuval Dor
DNA methylation at promoters is an important determinant of gene expression. Earlier studies suggested that the insulin gene promoter is uniquely unmethylated in insulin-expressing pancreatic β-cells, providing a classic example of this paradigm. Here we show that islet cells expressing insulin, glucagon, or somatostatin share a lack of methylation at the promoters of the insulin and glucagon genes. This is achieved by rapid demethylation of the insulin and glucagon gene promoters during differentiation of Neurogenin3+ embryonic endocrine progenitors, regardless of the specific endocrine cell-type chosen...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
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