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https://www.readbyqxmd.com/read/28654693/fatty-acid-synthase-reprograms-the-epigenome-in-uterine-leiomyosarcomas
#1
Min Guan, Xiwei Wu, Peiguo Chu, Warren A Chow
SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the "lipogenic phenotype of cancer." Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27...
2017: PloS One
https://www.readbyqxmd.com/read/28654248/multiplexed-sequence-specific-capture-of-chromatin-and-mass-spectrometric-discovery-of-associated-proteins
#2
Yunxiang Dai, Julia Kennedy-Darling, Michael R Shortreed, Mark Scalf, Audrey P Gasch, Lloyd M Smith
Comprehensive understanding of a gene's expression and regulation at the molecular level requires identification of all proteins interacting with the gene. HyCCAPP (Hybridization Capture of Chromatin Associated Proteins for Proteomics) is an approach that uses single-stranded DNA oligonucleotides to capture specific genomic sequences in cross-linked chromatin fragments, and identify associated proteins by mass spectrometry. Previous studies have shown HyCCAPP to provide useful information on protein-DNA interactions, revealing the proteins associated with the Gal1-10 region in yeast...
June 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28654055/chromatin-immunoprecipitation-chip-in-mouse-t-cell-lines
#3
Benedetto Daniele Giaimo, Francesca Ferrante, Tilman Borggrefe
Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants...
June 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28654021/vitamin-c-aging-and-alzheimer-s-disease
#4
REVIEW
Fiammetta Monacelli, Erica Acquarone, Chiara Giannotti, Roberta Borghi, Alessio Nencioni
Accumulating evidence in mice models of accelerated senescence indicates a rescuing role of ascorbic acid in premature aging. Supplementation of ascorbic acid appeared to halt cell growth, oxidative stress, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and extend lifespan. Interestingly, ascorbic acid (AA) was also found to positively modulate inflamm-aging and immunosenescence, two hallmarks of biological aging. Moreover, ascorbic acid has been shown to epigenetically regulate genome integrity and stability, indicating a key role of targeted nutrition in healthy aging...
June 27, 2017: Nutrients
https://www.readbyqxmd.com/read/28653981/the-role-of-replication-associated-repair-factors-on-r-loops
#5
REVIEW
Vaibhav Bhatia, Emilia Herrera-Moyano, Andrés Aguilera, Belén Gómez-González
The nascent RNA can reinvade the DNA double helix to form a structure termed the R-loop, where a single-stranded DNA (ssDNA) is accompanied by a DNA-RNA hybrid. Unresolved R-loops can impede transcription and replication processes and lead to genomic instability by a mechanism still not fully understood. In this sense, a connection between R-loops and certain chromatin markers has been reported that might play a key role in R-loop homeostasis and genome instability. To counteract the potential harmful effect of R-loops, different conserved messenger ribonucleoprotein (mRNP) biogenesis and nuclear export factors prevent R-loop formation, while ubiquitously-expressed specific ribonucleases and DNA-RNA helicases resolve DNA-RNA hybrids...
June 27, 2017: Genes
https://www.readbyqxmd.com/read/28653622/simultaneous-measurement-of-chromatin-accessibility-dna-methylation-and-nucleosome-phasing-in-single-cells
#6
Sebastian Pott
Gaining insights into the regulatory mechanisms that underlie the transcriptional variation observed between individual cells necessitates the development of methods that measure chromatin organization in single cells. Here I adapted Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) to measure chromatin accessibility and endogenous DNA methylation in single cells (scNOMe-seq). scNOMe-seq recovered characteristic accessibility and DNA methylation patterns at DNase hypersensitive sites (DHSs). An advantage of scNOMe-seq is that sequencing reads are sampled independently of the accessibility measurement...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28653617/replication-study-inhibition-of-bet-recruitment-to-chromatin-as-an-effective-treatment-for-mll-fusion-leukaemia
#7
Xiaochuan Shan, Juan Jose Fung, Alan Kosaka, Gwenn Danet-Desnoyers
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fung et al., 2015), that described how we intended to replicate selected experiments from the paper "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia" (Dawson et al., 2011). Here, we report the results of those experiments. We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition, whereas treatment of leukaemia cells harboring a different oncogenic driver (K-562 cell line) did not result in selective growth inhibition; this is similar to the findings reported in the original study (Figure 2A and Supplementary Figure 11A,B; Dawson et al...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28653353/preclinical-evaluation-of-the-bet-bromodomain-inhibitor-bay-1238097-for-the-treatment-of-lymphoma
#8
Elena Bernasconi, Eugenio Gaudio, Pascale Lejeune, Chiara Tarantelli, Luciano Cascione, Ivo Kwee, Filippo Spriano, Andrea Rinaldi, Afua A Mensah, Elaine Chung, Anastasios Stathis, Stephan Siegel, Norbert Schmees, Matthias Ocker, Emanuele Zucca, Bernard Haendler, Francesco Bertoni
The epigenome is often deregulated in cancer and treatment with inhibitors of bromodomain and extra-terminal proteins, the readers of epigenetic acetylation marks, represents a novel therapeutic approach. Here, we have characterized the anti-tumour activity of the novel bromodomain and extra-terminal (BET) inhibitor BAY 1238097 in preclinical lymphoma models. BAY 1238097 showed anti-proliferative activity in a large panel of lymphoma-derived cell lines, with a median 50% inhibitory concentration between 70 and 208 nmol/l...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28652620/differential-cohesin-loading-marks-paired-and-unpaired-regions-of-platypus-sex-chromosomes-at-prophase-i
#9
Aaron E Casey, Tasman J Daish, Jose Luis Barbero, Frank Grützner
Cohesins are vital for chromosome organisation during meiosis and mitosis. In addition to the important function in sister chromatid cohesion, these complexes play key roles in meiotic recombination, DSB repair, homologous chromosome pairing and segregation. Egg-laying mammals (monotremes) feature an unusually complex sex chromosome system, which raises fundamental questions about organisation and segregation during meiosis. We discovered a dynamic and differential accumulation of cohesins on sex chromosomes during platypus prophase I and specific reorganisation of the sex chromosome complex around a large nucleolar body...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28652613/flipping-between-polycomb-repressed-and-active-transcriptional-states-introduces-noise-in-gene-expression
#10
Gozde Kar, Jong Kyoung Kim, Aleksandra A Kolodziejczyk, Kedar Nath Natarajan, Elena Torlai Triglia, Borbala Mifsud, Sarah Elderkin, John C Marioni, Ana Pombo, Sarah A Teichmann
Polycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression; yet, there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of Polycomb repressive complex is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcription. Here, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28652379/the-mutant-p53-id4-complex-controls-vegfa-isoforms-by-recruiting-lncrna-malat1
#11
Magdalena Pruszko, Elisa Milano, Mattia Forcato, Sara Donzelli, Federica Ganci, Silvia Di Agostino, Simone De Panfilis, Francesco Fazi, David O Bates, Silvio Bicciato, Maciej Zylicz, Alicja Zylicz, Giovanni Blandino, Giulia Fontemaggi
The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin...
June 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28652207/characterizing-the-molecular-architectures-of-chromatin-modifying-complexes
#12
REVIEW
Dheva T Setiaputra, Calvin K Yip
Eukaryotic cells package their genome in the form of a DNA-protein complex known as chromatin. This organization not only condenses the genome to fit within the confines of the nucleus, but also provides a platform for a cell to regulate accessibility to different gene sequences. The basic packaging element of chromatin is the nucleosome, which consists of 146 base pairs of DNA wrapped around histone proteins. One major means that a cell regulates chromatin structure is by depositing post-translational modifications on nucleosomal histone proteins, and thereby altering internucleosomal interactions and/or binding to different chromatin associated factors...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28651105/heterogeneous-epigenetic-regulation-of-hace1-in-burkitt-lymphoma-derived-cells
#13
Abdelilah Bouzelfen, Hafid Kora, Marion Alcantara, Philippe Bertrand, Jean-Baptiste Latouche, Fabrice Jardin
We examined the consequences of 3-deazaneplanocin A (DZNep) on HACE1 expression in human Burkitt- Lymphoma-derived cells to investigate fundamental molecular mechanisms that control its expression. We treated the human Burkitt- Lymphoma-derived cells lines Ramos and Raji with DZNep and examined HACE1 mRNA expression by RT-PCR. We also studied the effect of DZNep on the methylation of lysine 9 and 27 of histone 3 (H3K27me3 and H3K9me2) associated with the CpG88 and CpG177 islands of the HACE1 promoters by chromatin immunoprecipitation and quantitative PCR...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28650521/jmj27-an-arabidopsis-h3k9-histone%C3%A2-demethylase-modulates-defense-against-pseudomonas-syringae%C3%A2-and%C3%A2-flowering%C3%A2-time
#14
Aditya Dutta, Pratibha Choudhary, Julie Caruana, Ramesh Raina
Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time...
June 26, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28650470/signaling-coupled-epigenomic-regulation-of-gene-expression
#15
REVIEW
R Kumar, S Deivendran, T R Santhoshkumar, M R Pillai
Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650433/the-evening-complex-coordinates-environmental-and-endogenous-signals-in-arabidopsis
#16
Daphne Ezer, Jae-Hoon Jung, Hui Lan, Surojit Biswas, Laura Gregoire, Mathew S Box, Varodom Charoensawan, Sandra Cortijo, Xuelei Lai, Dorothee Stöckle, Chloe Zubieta, Katja E Jaeger, Philip A Wigge
Plants maximize their fitness by adjusting their growth and development in response to signals such as light and temperature. The circadian clock provides a mechanism for plants to anticipate events such as sunrise and adjust their transcriptional programmes. However, the underlying mechanisms by which plants coordinate environmental signals with endogenous pathways are not fully understood. Using RNA-sequencing and chromatin immunoprecipitation sequencing experiments, we show that the evening complex (EC) of the circadian clock plays a major role in directly coordinating the expression of hundreds of key regulators of photosynthesis, the circadian clock, phytohormone signalling, growth and response to the environment...
June 26, 2017: Nature Plants
https://www.readbyqxmd.com/read/28650429/acetate-mediated-novel-survival-strategy-against-drought-in-plants
#17
Jong-Myong Kim, Taiko Kim To, Akihiro Matsui, Keitaro Tanoi, Natsuko I Kobayashi, Fumio Matsuda, Yoshiki Habu, Daisuke Ogawa, Takuya Sakamoto, Sachihiro Matsunaga, Khurram Bashir, Sultana Rasheed, Marina Ando, Hiroko Takeda, Kanako Kawaura, Miyako Kusano, Atsushi Fukushima, Takaho A Endo, Takashi Kuromori, Junko Ishida, Taeko Morosawa, Maho Tanaka, Chieko Torii, Yumiko Takebayashi, Hitoshi Sakakibara, Yasunari Ogihara, Kazuki Saito, Kazuo Shinozaki, Alessandra Devoto, Motoaki Seki
Water deficit caused by global climate changes seriously endangers the survival of organisms and crop productivity, and increases environmental deterioration(1,2). Plants' resistance to drought involves global reprogramming of transcription, cellular metabolism, hormone signalling and chromatin modification(3-8). However, how these regulatory responses are coordinated via the various pathways, and the underlying mechanisms, are largely unknown. Herein, we report an essential drought-responsive network in which plants trigger a dynamic metabolic flux conversion from glycolysis into acetate synthesis to stimulate the jasmonate (JA) signalling pathway to confer drought tolerance...
June 26, 2017: Nature Plants
https://www.readbyqxmd.com/read/28650317/serine-adp-ribosylation-reversal-by-the-hydrolase-arh3
#18
Ivan Ahel, Pietro Fontana, Juan José Bonfiglio, Luca Palazzo, Edward Bartlett, Ivan Matic
ADP-ribosylation (ADPr) is a posttranslational modification (PTM) of proteins that controls many cellular processes, including DNA repair, transcription, chromatin regulation and mitosis. A number of proteins catalyse the transfer and hydrolysis of ADPr, and also specify how and when the modification is conjugated to the targets. We recently discovered a new form of ADPr that is attached to serine residues in target proteins (Ser-ADPr) and showed that this PTM is specifically made by PARP1/HPF1 and PARP2/HPF1 complexes...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650265/autophagy-regulates-dna-repair-through-sqstm1-p62
#19
Yuchen Feng, Daniel J Klionsky
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin...
June 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28649990/a-pan-cancer-genome-wide-analysis-reveals-tumour-dependencies-by-induction-of-nonsense-mediated-decay
#20
Zhiyuan Hu, Christopher Yau, Ahmed Ashour Ahmed
Nonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply it on somatic mutations reported in The Cancer Genome Atlas. We identify more than 73 K mutations that are predicted to elicit NMD (NMD-elicit). NMD-elicit mutations in tumour suppressor genes (TSGs) are associated with significant reduction in gene expression...
June 26, 2017: Nature Communications
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