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https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#1
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
March 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28343628/functional-architectures-of-local-and-distal-regulation-of-gene-expression-in-multiple-human-tissues
#2
Xuanyao Liu, Hilary K Finucane, Alexander Gusev, Gaurav Bhatia, Steven Gazal, Luke O'Connor, Brendan Bulik-Sullivan, Fred A Wright, Patrick F Sullivan, Benjamin M Neale, Alkes L Price
Genetic variants that modulate gene expression levels play an important role in the etiology of human diseases and complex traits. Although large-scale eQTL mapping studies routinely identify many local eQTLs, the molecular mechanisms by which genetic variants regulate expression remain unclear, particularly for distal eQTLs, which these studies are not well powered to detect. Here, we leveraged all variants (not just those that pass stringent significance thresholds) to analyze the functional architecture of local and distal regulation of gene expression in 15 human tissues by employing an extension of stratified LD-score regression that produces robust results in simulations...
March 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28341773/pml-protein-organizes-heterochromatin-domains-where-it-regulates-histone-h3-3-deposition-by-atrx-daxx
#3
Erwan Delbarre, Kristina Ivanauskiene, Jane Spirkoski, Akshay Shah, Kristin Vekterud, Jan Øivind Moskaug, Stig Ove Bøe, Lee Wong, Thomas Küntziger, Philippe Collas
Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains is largely undeciphered. We report here a role of promyelocytic leukemia (PML) protein in routing histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains which we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28338761/influence-of-polynucleosome-preparation-methods-on-sedimentation-velocity-analysis-of-chromatin
#4
Tomoya Kujirai, Shinichi Machida, Akihisa Osakabe, Hitoshi Kurumizaka
Chromatin dynamics and higher order structures play essential roles in genomic DNA functions. Histone variants and histone post-translational modifications are involved in the regulation of chromatin structure and dynamics, cooperatively with DNA methylation and chromatin binding proteins. Therefore, studies of higher-order chromatin conformations have become important to reveal how genomic DNA is regulated during DNA transcription, replication, recombination and repair. The sedimentation velocity analysis by analytical ultracentrifugation has been commonly used to evaluate the higher-order conformation of in vitro reconstituted polynucleosomes, as model chromatin...
December 22, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/28334823/h3-y-discriminates-between-hira-and-daxx-chaperone-complexes-and-reveals-unexpected-insights-into-human-daxx-h3-3-h4-binding-and-deposition-requirements
#5
Lisa-Maria Zink, Erwan Delbarre, H Christian Eberl, Eva C Keilhauer, Clemens Bönisch, Sebastian Pünzeler, Marek Bartkuhn, Philippe Collas, Matthias Mann, Sandra B Hake
Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28329910/nucleosome-mobility-and-the-regulation-of-gene-expression-insights-from-single-molecule-studies
#6
REVIEW
Sergei Rudnizky, Omri Malik, Adaiah Bavly, Lilach Pnueli, Philippa Melamed, Ariel Kaplan
Nucleosomes at the promoters of genes regulate the accessibility of the transcription machinery to DNA, and function as a basic layer in the complex regulation of gene expression. Our understanding of the role of the nucleosome's spontaneous, thermally driven position changes in modulating expression is lacking. This is the result of the paucity of experimental data on these dynamics, at high-resolution, and for DNA sequences that belong to real, transcribed genes. We have developed an assay that uses partial, reversible unzipping of nucleosomes with optical tweezers to repeatedly probe a nucleosome's position over time...
March 22, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28320872/the-drosophila-daxx-like-protein-dlp-cooperates-with-asf1-for-h3-3-deposition-and-heterochromatin-formation
#7
Catherine Fromental-Ramain, Philippe Ramain, Ali Hamiche
Histone variants are non-allelic isoforms of canonical histones and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of Drosophila DAXX Like Protein (DLP) by using both fly genetics approaches and protein biochemistry...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28319067/the-histone-demethylase-kdm3a-and-its-downstream-target-mcam-promote-ewing-sarcoma-cell-migration-and-metastasis
#8
M Sechler, J K Parrish, D K Birks, P Jedlicka
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317148/bortezomib-induced-peripheral-neuropathy-a-genome-wide-association-study-on-multiple-myeloma-patients
#9
Chiara Campo, Miguel Inacio da Silva Filho, Niels Weinhold, Seyed Hamidreza Mahmoudpour, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment...
March 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28315825/effects-of-florida-red-tides-on-histone-variant-expression-and-dna-methylation-in-the-eastern-oyster-crassostrea-virginica
#10
Rodrigo Gonzalez-Romero, Victoria Suarez-Ulloa, Javier Rodriguez-Casariego, Daniel Garcia-Souto, Gabriel Diaz, Abraham Smith, Juan Jose Pasantes, Gary Rand, Jose M Eirin-Lopez
Massive algal proliferations known as Harmful Algal Blooms (HABs) represent one of the most important threats to coastal areas. Among them, the so-called Florida Red Tides (FRTs, caused by blooms of the dinoflagellate Karenia brevis and associated brevetoxins) are particularly detrimental in the southeastern U.S., causing high mortality rates and annual losses in excess of $40 million. The ability of marine organisms to cope with environmental stressors (including those produced during HABs) is influenced by genetic and epigenetic mechanisms, the latter resulting in phenotypic changes caused by heritable modifications in gene expression, without involving changes in the genetic (DNA) sequence...
March 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28314753/transethnic-meta-analysis-identifies-gsdma-and-prdm1-as-susceptibility-genes-to-systemic-sclerosis
#11
Chikashi Terao, Takahisa Kawaguchi, Philippe Dieude, John Varga, Masataka Kuwana, Marie Hudson, Yasushi Kawaguchi, Marco Matucci-Cerinic, Koichiro Ohmura, Gabriela Riemekasten, Aya Kawasaki, Paolo Airo, Tetsuya Horita, Akira Oka, Eric Hachulla, Hajime Yoshifuji, Paola Caramaschi, Nicolas Hunzelmann, Murray Baron, Tatsuya Atsumi, Paul Hassoun, Takeshi Torii, Meiko Takahashi, Yasuharu Tabara, Masakazu Shimizu, Akiko Tochimoto, Naho Ayuzawa, Hidetoshi Yanagida, Hiroshi Furukawa, Shigeto Tohma, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Toshiyuki Yamamoto, Daisuke Goto, Yoshihide Asano, Masatoshi Jinnin, Hirahito Endo, Hiroki Takahashi, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn, Soumya Raychaudhuri, Katherine Liao, Peter Gregersen, Naoyuki Tsuchiya, Valeria Riccieri, Inga Melchers, Gabriele Valentini, Anne Cauvet, Maria Martinez, Tsuneyo Mimori, Fumihiko Matsuda, Yannick Allanore
OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28304185/modulation-of-transcription-factor-binding-and-epigenetic-regulation-of-the-mlh1-cpg-island-and-shore-by-polymorphism-rs1800734-in-colorectal-cancer
#12
Andrea J Savio, Bharati Bapat
The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG)...
March 17, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28301528/genome-wide-mapping-of-histone-h3k9me2-in-acute-myeloid-leukemia-reveals-large-chromosomal-domains-associated-with-massive-gene-silencing-and-sites-of-genome-instability
#13
Anna C Salzberg, Abigail Harris-Becker, Evgenya Y Popova, Nikki Keasey, Thomas P Loughran, David F Claxton, Sergei A Grigoryev
A facultative heterochromatin mark, histone H3 lysine 9 dimethylation (H3K9me2), which is mediated by histone methyltransferases G9a/GLP (EHMT2/1), undergoes dramatic rearrangements during myeloid cell differentiation as observed by chromatin imaging. To determine whether these structural transitions also involve genomic repositioning of H3K9me2, we used ChIP-sequencing to map genome-wide topography of H3K9me2 in normal human granulocytes, normal CD34+ hematopoietic progenitors, primary myeloblasts from acute myeloid leukemia (AML) patients, and a model leukemia cell line K562...
2017: PloS One
https://www.readbyqxmd.com/read/28298601/simultaneous-single-cell-in-situ-analysis-of-human-adenovirus-type-5-dna-and-mrna-expression-patterns-in-lytic-and-persistent-infection
#14
Tomasz Krzywkowski, Sibel Ciftci, Farzaneh Assadian, Mats Nilsson, Tanel Punga
An efficient adenovirus infection results in high-level accumulation of viral DNA and mRNAs in the infected cell population. However, the average viral DNA and mRNA content in a heterogeneous cell population do not necessarily reflect the same abundance in individual cells. Here we describe a novel padlock probe-based rolling circle amplification technique that enables simultaneous detection and analysis of human adenovirus type 5 (HAdV-5) genomic DNA and virus-encoded mRNAs in individual infected cells. We demonstrate that the method is applicable for detection and quantification of HAdV-5 DNA and mRNAs in short-term infections in human epithelial cells and in long-term infections in human B lymphocytes...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28298478/phylogeny-based-systematization-of-arabidopsis-proteins-with-histone-h1-globular-domain
#15
Maciej Kotliński, Łukasz Knizewski, Anna Muszewska, Kinga Rutowicz, Maciej Lirski, Anja Schmidt, Celia Baroux, Krzysztof Ginalski, Andrzej Jerzmanowski
H1 (or linker) histones are basic nuclear proteins that possess an evolutionarily-conserved nucleosome-binding globular domain - GH1. They perform critical functions in determining the accessibility of chromatin DNA to trans-acting factors. In most metazoan species so far studied, linker histones are highly heterogeneous, with numerous non-allelic variants co-occurring in the same cells. The phylogenetic relationships among these variants as well as their structural and functional properties have been relatively well established...
March 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28298436/chromatin-remodeler-chd4-represses-aberrant-expression-of-tbx3-and-sustains-self-renewal-of-embryonic-stem-cells
#16
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of a series of transcriptional factors and epigenetic modulators. However, molecular mechanisms underlying the function of these regulators are not fully elucidated. Chd4, an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in the regulation of ESC properties remains elusive...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296507/lncrna-pvt1-epigenetically-silences-mir-195-and-modulates-emt-and-chemoresistance-in-cervical-cancer-cells
#17
Ching-Ju Shen, Ya-Min Cheng, Chiu-Lin Wang
The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in-vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region...
March 15, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28295392/erecta-signaling-controls-arabidopsis-inflorescence-architecture-through-chromatin-mediated-activation-of-pre1-expression
#18
Hanyang Cai, Lihua Zhao, Lulu Wang, Man Zhang, Zhenxia Su, Yan Cheng, Heming Zhao, Yuan Qin
Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied...
March 13, 2017: New Phytologist
https://www.readbyqxmd.com/read/28293299/identification-of-epigenetic-signature-associated-with-alpha-thalassemia-mental-retardation-x-linked-syndrome
#19
Laila C Schenkel, Kristin D Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic
BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the ATRX gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28290676/biochemical-characterization-of-ap-lyase-and-m-6-a-demethylase-activities-of-human-alkb-homolog-1-alkbh1
#20
Tina A Müller, Michael A Tobar, Madison N Perian, Robert P Hausinger
Alkbh1 is one of nine mammalian homologs of Escherichia coli AlkB, a 2-oxoglutarate-dependent dioxygenase that catalyzes direct DNA repair by removing alkyl lesions from DNA. Six distinct enzymatic activities have been reported for Alkbh1, including hydroxylation of variously methylated DNA, mRNA, tRNA, or histone substrates along with the cleavage of DNA at apurinic/apyrimidinic (AP) sites followed by covalent attachment to the 5'-product. The studies described here extend the biochemical characterization for two of these enzymatic activities using human ALKBH1: the AP lyase and 6-methyl adenine DNA demethylase activities...
March 14, 2017: Biochemistry
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