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https://www.readbyqxmd.com/read/28723896/maternal-h3k27me3-controls-dna-methylation-independent-imprinting
#1
Azusa Inoue, Lan Jiang, Falong Lu, Tsukasa Suzuki, Yi Zhang
Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashions. After fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci, including imprinting control regions. How parental chromatin becomes equalized and how imprinting control regions escape from this reprogramming is largely unknown. Here we profile parental allele-specific DNase I hypersensitive sites in mouse zygotes and morula embryos, and investigate the epigenetic mechanisms underlying these allelic sites...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#2
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723639/integrated-analysis-of-the-molecular-action-of-vorinostat-identifies-epi-sensitised-targets-for-combination-therapy
#3
Jodie F Hay, Katrina Lappin, Fabio Liberante, Laura M Kettyle, Kyle B Matchett, Alexander Thompson, Ken I Mills
Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723630/functional-role-of-setd2-bap1-parp-3-and-pbrm1-candidate-genes-on-the-regulation-of-htert-gene-expression
#4
Hannah Linne, Hemad Yasaei, Alison Marriott, Amanda Harvey, Kefah Mokbel, Robert Newbold, Terry Roberts
Narrowing the search for the critical hTERT repressor sequence(s) has identified three regions on chromosome 3p (3p12-p21.1, 3p21.2 and 3p21.3-p22). However, the precise location and identity of the sequence(s) responsible for hTERT transcriptional repression remains elusive. In order to identify critical hTERT repressor sequences located within human chromosome 3p12-p22, we investigated hTERT transcriptional activity within 21NT microcell hybrid clones containing chromosome 3 fragments. Mapping of chromosome 3 structure in a single hTERT-repressed 21NT-#3fragment hybrid clone, revealed a 490kb region of deletion localised to 3p21...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#5
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723572/robust-identification-of-developmentally-active-endothelial-enhancers-in-zebrafish-using-fans-assisted-atac-seq
#6
Aurelie Quillien, Mary Abdalla, Jun Yu, Jianhong Ou, Lihua Julie Zhu, Nathan D Lawson
Identification of tissue-specific and developmentally active enhancers provides insights into mechanisms that control gene expression during embryogenesis. However, robust detection of these regulatory elements remains challenging, especially in vertebrate genomes. Here, we apply fluorescent-activated nuclei sorting (FANS) followed by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to identify developmentally active endothelial enhancers in the zebrafish genome. ATAC-seq of nuclei from Tg(fli1a:egfp)(y1) transgenic embryos revealed expected patterns of nucleosomal positioning at transcriptional start sites throughout the genome and association with active histone modifications...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#7
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#8
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723212/engineering-recombinant-protein-sensors-for-quantifying-histone-acetylation
#9
Oscar F Sanchez, Agnes Mendonca, Ana D Carneiro, Chongli Yuan
H3K14ac (acetylation of lysine 14 of histone H3) is one of the most important epigentic modifications. Aberrant changes in H3K14ac have been associated with various diseases, including cancers and neurological disorders. Tools that enable detection and quantification of H3K14ac levels in cell extracts and in situ are thus of critical importance to reveal its role in various biological processes. Current detection techniques of specific histone modifications, however, are constrained by tedious sample pretreatments, lack of quantitative accuracy, and reliance on high quality antibodies...
March 24, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#10
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722229/a-transposon-directed-epigenetic-change-in-zmcct-underlies-quantitative-resistance-to-gibberella-stalk-rot-in-maize
#11
Chao Wang, Qin Yang, Weixiang Wang, Yipu Li, Yanling Guo, Dongfeng Zhang, Xuena Ma, Wei Song, Jiuran Zhao, Mingliang Xu
A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#12
J Choi, S Y Park, T K Kwon, S-I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28720596/elongator-regulates-hypocotyl-growth-in-darkness-and-during-photomorphogenesis
#13
Magdalena Woloszynska, Olimpia Gagliardi, Filip Vandenbussche, Steven De Groeve, Luis Alonso Baez, Pia Neyt, Sabine Le Gall, Jorge Fung, Paloma Mas, Dominique Van Der Straeten, Mieke Van Lijsebettens
Elongator promotes RNA polymerase II-mediated transcript elongation through epigenetic activities such as histone acetylation. Elongator regulates growth, development, immune response, sensitivity to drought and abscisic acid. We demonstrate that elo mutants exhibit defective hypocotyl elongation but have a normal apical hook in darkness and are hyposensitive to light during photomorphogenesis. These elo phenotypes are supported by transcriptome changes, i.e. downregulation of circadian clock components, positive regulators of skoto- or photomorphogenesis, hormonal pathways and cell wall biogenesis-related factors...
July 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28720588/ews-fli-is-a-master-regulator-of-metabolic-reprogramming-in-ewing-sarcoma
#14
Jason M Tanner, Claire Bensard, Peng Wei, Nathan M Krah, John C Schell, Jamie D Gardiner, Joshua D Schiffman, Stephen L Lessnick, Jared Rutter
Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology...
July 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28720579/recruitment-of-histone-modifications-to-assist-mrna-dosage-maintenance-after-degeneration-of-cytosine-dna-methylation-during-animal-evolution
#15
Andrew Yf Chang, Ben-Yang Liao
Following gene duplication, mRNA expression of the duplicated gene is reduced to maintain mRNA dosage. In mammals, this process is achieved with increased cytosine DNA methylation of the promoters of duplicated genes to suppress transcriptional initiation. However, not all animal species possess a full apparatus for cytosine DNA methylation. For such species such as roundworm (Caenorhabditis elegans, "worm" hereafter) or fruit fly (Drosophila melanogaster, "fly" hereafter), it is unclear how reduced expression of duplicated genes has been achieved evolutionarily...
July 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28720390/epigenetic-regulation-of-epithelial-to-mesenchymal-transition-by-the-lysine-specific-demethylase-lsd1-kdm1a
#16
REVIEW
Susanna Ambrosio, Carmen D Saccà, Barbara Majello
The Lysine-specific demethylase 1, KDM1A/LSD1, plays a central role in the regulation of Pol II transcription through the removal of the activation mark (mono- and dimethyl lysine 4 of histone H3). LSD1 is often deregulated in human cancers, and it is frequently overexpressed in human solid cancers and leukemia. LSD1 regulates the epithelial mesenchymal transition (EMT) in epithelial cells, i.e., the ability to transition into mesenchymal cells, to lose homotypic adhesion and to acquire migratory capacity. From its initial discovery as a component of the Snail complex, multiple studies highlighted the causative role of LSD1 in cell invasiveness and EMT, describing its direct involvement in different molecular processes through the interaction with specific partners...
July 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28720323/rapid-divergence-of-histones-in-hydrozoa-cnidaria-and-evolution-of-a-novel-histone-involved-in-dna-damage-response-in-hydra
#17
Puli Chandramouli Reddy, Suyog Ubhe, Neha Sirwani, Rasika Lohokare, Sanjeev Galande
Histones are fundamental components of chromatin in all eukaryotes. Hydra, an emerging model system belonging to the basal metazoan phylum Cnidaria, provides an ideal platform to understand the evolution of core histone components at the base of eumetazoan phyla. Hydra exhibits peculiar properties such as tremendous regenerative capacity, lack of organismal senescence and rarity of malignancy. In light of the role of histone modifications and histone variants in these processes it is important to understand the nature of histones themselves and their variants in hydra...
June 15, 2017: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#18
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28719581/phosphorylated-hbo1-at-uv-irradiated-sites-is-essential-for-nucleotide-excision-repair
#19
Hiroyuki Niida, Ryoichi Matsunuma, Ryo Horiguchi, Chiharu Uchida, Yuka Nakazawa, Akira Motegi, Koji Nishimoto, Satoshi Sakai, Tatsuya Ohhata, Kyoko Kitagawa, Shinichi Moriwaki, Hideo Nishitani, Ayako Ui, Tomoo Ogi, Masatoshi Kitagawa
HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28719070/sirtuin-1-attenuates-inflammation-and-hepatocellular-damage-in-liver-transplant-ischemia-reperfusion-from-mouse-to-human
#20
Kojiro Nakamura, Shoichi Kageyama, Bibo Ke, Takehiro Fujii, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI), an inevitable antigen-independent inflammation response in cadaveric liver transplantation, correlates with poor early graft function, rejection episodes, and contributes to donor organ shortage. Sirtuin 1 (SIRT1) is a histone deacetylase which may regulate inflammatory cell activity and manage liver function in IRI, though its functional role and clinical relevance remains to be elucidated. We investigated the efficacy of SIRT1 activation in murine liver IRI model and verified the concept of putative SIRT1-mediated hepatoprotection in clinical liver transplantation...
July 18, 2017: Liver Transplantation
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