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https://www.readbyqxmd.com/read/29339785/the-lncrna-gata6-as-epigenetically-regulates-endothelial-gene-expression-via-interaction-with-loxl2
#1
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A Boon, Stefanie Dimmeler
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29335024/sex-differences-in-the-late-first-trimester-human-placenta-transcriptome
#2
Tania L Gonzalez, Tianyanxin Sun, Alexander F Koeppel, Bora Lee, Erica T Wang, Charles R Farber, Stephen S Rich, Lauren W Sundheimer, Rae A Buttle, Yii-Der Ida Chen, Jerome I Rotter, Stephen D Turner, John Williams, Mark O Goodarzi, Margareta D Pisarska
BACKGROUND: Development of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood. METHODS: RNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males)...
January 15, 2018: Biology of Sex Differences
https://www.readbyqxmd.com/read/29325110/impact-of-genetic-risk-loci-for-multiple-sclerosis-on-expression-of-proximal-genes-in-patients
#3
Tojo James, Magdalena Lindén, Hiromasa Morikawa, Sunjay Jude Fernandes, Sabrina Ruhrmann, Mikael Huss, Maya Brandi, Fredrik Piehl, Maja Jagodic, Jesper Tegnér, Mohsen Khademi, Tomas Olsson, David Gomez-Cabrero, Ingrid Kockum
Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS). Since a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells (PBMCs) from MS patients (n = 145) to identify eQTLs in regions centered on 109 MS risk SNPs and seven associated HLA variants...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29322219/sirt6-mediated-transcriptional-suppression-of-txnip-is-critical-for-pancreatic-beta-cell-function-and-survival-in-mice
#4
Kunhua Qin, Ning Zhang, Zhao Zhang, Michael Nipper, Zhenxin Zhu, Jake Leighton, Kexin Xu, Nicolas Musi, Pei Wang
AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system...
January 10, 2018: Diabetologia
https://www.readbyqxmd.com/read/29321829/dna-methylation-in-stroke-update-of-latest-advances
#5
REVIEW
Jerzy Krupinski, Caty Carrera, Elena Muiño, Nuria Torres, Raid Al-Baradie, Natalia Cullell, Israel Fernandez-Cadenas
Epigenetic modifications are hereditable and modifiable factors that do not alter the DNA sequence. These epigenetic factors include DNA methylation, acetylation of histones and non-coding RNAs. Epigenetic factors have mainly been associated with cancer but also with other diseases and conditions such as diabetes or obesity. In addition, epigenetic modifications could play an important role in cardiovascular diseases, including stroke. We review the latest advances in stroke epigenetics, focusing on DNA methylation studies and the future perspectives in this field...
2018: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#6
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29310890/the-latest-twists-in-chromatin-remodeling
#7
REVIEW
Ralf Blossey, Helmut Schiessel
In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation...
January 5, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29310033/epigenetic-mechanisms-in-odontogenic-tumors-a-literature-review
#8
REVIEW
Jorge Sandoval-Basilio, Rogelio González-González, Ronell Bologna-Molina, Mario Isiordia-Espinoza, Gabriela Leija-Montoya, Sofia L Alcaraz-Estrada, Idanya Serafín-Higuera, Javier González-Ramírez, Nicolás Serafín-Higuera
OBJECTIVE: Epigenetic mechanisms, such as DNA methylation, regulate important biological processes as gene expression and it was suggested that these phenomena play important roles in the carcinogenesis and tumor biology. The aim of this review is to provide the current state of knowledge about epigenetic alterations, focusing mainly on DNA methylation, reported in odontogenic tumors. DESIGN: Literatures were searched based in the combination of the following keywords: odontogenic tumors, epigenetics, DNA methylation, histone modifications, non-coding RNA, microRNA, DNA methyltransferases...
December 30, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29304334/beyond-the-histone-code-a-physical-map-of-chromatin-states
#9
Iva A Tchasovnikarova, Robert E Kingston
Post-translational modifications of histones are widely used to discriminate between different types of chromatin. In a recent issue of Molecular Cell, Becker et al. (2017) delineate chromatin states based on physical properties, thereby expanding our understanding of chromatin function.
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29298432/characterizing-zc3h18-a-multi-domain-protein-at-the-interface-of-rna-production-and-destruction-decisions
#10
Kinga Winczura, Manfred Schmid, Claudia Iasillo, Kelly R Molloy, Lea Mørch Harder, Jens S Andersen, John LaCava, Torben Heick Jensen
Nuclear RNA metabolism is influenced by protein complexes connecting to both RNA-productive and -destructive pathways. The ZC3H18 protein binds the cap-binding complex (CBC), universally present on capped RNAs, while also associating with the nuclear exosome targeting (NEXT) complex, linking to RNA decay. To dissect ZC3H18 function, we conducted interaction screening and mutagenesis of the protein, which revealed a phosphorylation-dependent isoform. Surprisingly, the modified region of ZC3H18 associates with core histone proteins...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29286490/a-facile-protocol-to-generate-site-specifically-acetylated-proteins-in-escherichia-coli
#11
Sumana Venkat, Caroline Gregory, Kexin Meng, Qinglei Gan, Chenguang Fan
Post-translational modifications that occur at specific positions of proteins have been shown to play important roles in a variety of cellular processes. Among them, reversible lysine acetylation is one of the most widely distributed in all domains of life. Although numerous mass spectrometry-based acetylome studies have been performed, further characterization of these putative acetylation targets has been limited. One possible reason is that it is difficult to generate purely acetylated proteins at desired positions by most classic biochemical approaches...
December 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285183/targeting-microrna-uhrf1-pathways-as-a-novel-strategy-for-cancer-therapy
#12
Hani Choudhry, Mazin A Zamzami, Ziad Omran, Wei Wu, Marc Mousli, Christian Bronner, Mahmoud Alhosin
Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA methyltransferase, histone deacetylase 1, histone acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29281093/large-scale-determination-and-characterization-of-cell-type-specific-regulatory-elements-in-the-human-genome
#13
Can Wang, Shihua Zhang
Histone modifications have been widely elucidated to play vital roles in gene regulation and cell identity. The Roadmap Epigenomics Consortium generated a reference catalogue of several key histone modifications across > 100s of human cell types and tissues. Decoding these epigenomes into functional regulatory elements is a challenging task in computational biology. To this end, we adopted a differential chromatin modification analysis framework to comprehensively determine and characterize cell type-specific regulatory elements (CSREs) and their histone modification codes in the human epigenomes of five histone modifications across 127 tissues or cell types...
December 21, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29279287/histone-modifiers-dynamic-regulators-of-the-cutaneous-transcriptome
#14
Kanad Ghosh, Kyle O'Neil, Brian C Capell
By regulating the accessibility of the genome, epigenetic regulators such as histone proteins and the chromatin-modifying enzymes that act upon them control gene expression. Proper regulation of this "histone code" allows for the precise control of transcriptional networks that are essential for establishing and maintaining cell fate and identity, disruption of which may drive carcinogenesis. How these dynamic epigenetic regulators contribute to both skin homeostasis and disease is only beginning to be understood...
December 18, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29279257/epigenetic-changes-in-headache
#15
M S Cámara, M Martín Bujanda, M Mendioroz Iriarte
INTRODUCTION: Multiple factors, including both genetic and environmental mechanisms, appear to play a role in the aetiology of headache. An interesting area of study is the possible involvement of epigenetic mechanisms in headache development and the transformation to chronic headache, and the potential role of these factors as a therapeutic target. METHODS: We performed a literature review of the involvement of different epigenetic mechanisms in headache, mainly using the Medline/PubMed database...
December 23, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29275200/long-non-coding-rna-ccal-promotes-hepatocellular-carcinoma-progression-by-regulating-ap-2%C3%AE-and-wnt-%C3%AE-catenin-pathway
#16
Yu Liu, Ye Yang, Tianlong Wang, Li Wang, Xin Wang, Tiemin Li, Yue Shi, Yawei Wang
OBJECTIVE: Long non-coding RNAs are emerging as key molecules in cancer progression. LncRNA-CCAL has shown to be highly expressed and important in regulating CRC and osteosarcoma development. Nevertheless, the expression and mechanism of CCAL in HCC is still not well understood. METHODS: qRT-PCR and ISH were used to evaluate CCAL expression in HCC tissues and cell lines. Histone H3 methylation and acetylation levels across CCAL promoter region were examined by chromatin immunoprecipitation assays...
December 21, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29248574/lncrna-uca1-attenuates-autophagy-dependent-cell-death-through-blocking-autophagic-flux-under-arsenic-stress
#17
Ming Gao, Changying Li, Ming Xu, Yun Liu, Sijin Liu
Arsenic (As) is a naturally toxin which exists ubiquitously in foods and various environment media, incurring diverse toxicities and health problems. Previous studies have shown that oxidative stress, genotoxic damage and pro-apoptotic pathways are ascribed to As-associated detrimental effects. Meanwhile, epigenetic regulations (such as miRNAs and histone modifications) were also reported to contribute to As-induced adverse effects. Nonetheless, whether long non-coding RNAs (LncRNAs) are indispensable for the regulation of As-induced biological outcomes are nearly unknown...
December 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29244246/role-of-rna-modifications-in-brain-and-behavior
#18
REVIEW
Kornel E Schuebel, Yonwoo Jung, David Goldman
Much progress in our understanding of RNA metabolism has been made since the first RNA modification was identified in 1957. To date, more than 100 distinct chemical modifications have been identified, and more await discovery. Many of these modifications are found in non-coding RNAs but recent studies suggest an important role for RNA modification in coding RNAs as well. Here we summarize current knowledge of cellular consequences of RNA modifications, with a special emphasis on neuropsychiatric disorders. We present evidence for the existence of an "RNA code", similar to the histone code, that fine-tunes gene expression in the nervous system by using combinations of different RNA modifications...
December 15, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29240919/genome-wide-dose-dependent-inhibition-of-histone-deacetylases-studies-reveal-their-roles-in-enhancer-remodeling-and-suppression-of-oncogenic-super-enhancers
#19
Gilson J Sanchez, Phillip A Richmond, Eric N Bunker, Samuel S Karman, Joseph Azofeifa, Aaron T Garnett, Quanbin Xu, Graycen E Wheeler, Cathryn M Toomey, Qinghong Zhang, Robin D Dowell, Xuedong Liu
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29234025/h3k14ac-is-linked-to-methylation-of-h3k9-by-the-triple-tudor-domain-of-setdb1
#20
Renata Z Jurkowska, Su Qin, Goran Kungulovski, Wolfram Tempel, Yanli Liu, Pavel Bashtrykov, Judith Stiefelmaier, Tomasz P Jurkowski, Srikanth Kudithipudi, Sara Weirich, Raluca Tamas, Hong Wu, Ludmila Dombrovski, Peter Loppnau, Richard Reinhardt, Jinrong Min, Albert Jeltsch
SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2...
December 12, 2017: Nature Communications
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