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https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#1
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/28722229/a-transposon-directed-epigenetic-change-in-zmcct-underlies-quantitative-resistance-to-gibberella-stalk-rot-in-maize
#2
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/28717009/acetylation-on-histone-h3-lysine-9-mediates-a-switch-from-transcription-initiation-to-elongation
#3
Leah A Gates, Jiejun Shi, Aarti D Rohira, Qin Feng, Bokai Zhu, Mark T Bedford, Cari A Sagum, Sung Yun Jung, Jun Qin, Ming-Jer Tsai, Sophia Y Tsai, Wei Li, Charles E Foulds, Bert W O'Malley
The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (Pol II) to escape promoter proximal pausing on chromatin. While elongation factors promote pause release leading to transcription elongation, the role of epigenetic modifications during this critical transition step is poorly understood. Two histone marks on histone H3, lysine 4 trimethylation (H3K4me3) and lysine 9 acetylation (H3K9ac), co-localize on active gene promoters and are associated with active transcription...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28712943/sex-and-brain-region-specific-effects-of-prenatal-stress-and-lead-exposure-on-permissive-and-repressive-post-translational-histone-modifications-from-embryonic-development-through-adulthood
#4
G Varma, M Sobolewski, D A Cory-Slechta, J S Schneider
Developmental exposure to prenatal stress (PS) and lead (Pb) can affect brain development and adversely influence behavior and cognition. Epigenetic-based gene regulation is crucial for normal brain development and mis-regulation, in any form, can result in neurodevelopmental disorders. Post-translational histone modifications (PTHMs) are an integral and dynamic component of the epigenetic machinery involved in gene regulation. Exposures to Pb and/or PS may alter PTHM profiles, promoting lifelong alterations in brain function observed following Pb±PS exposure...
July 13, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28708824/tex19-1-promotes-spo11-dependent-meiotic-recombination-in-mouse-spermatocytes
#5
James H Crichton, Christopher J Playfoot, Marie MacLennan, David Read, Howard J Cooke, Ian R Adams
Meiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that the mammal-specific gene Tex19.1 promotes Spo11-dependent recombination in mouse spermatocytes. We show that the chromosome asynapsis previously reported in Tex19...
July 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28706445/histone-demethylase-kdm2b-upregulates-histone-methyltransferase-ezh2-expression-and-contributes-to-the-progression-of-ovarian-cancer-in-vitro-and-in-vivo
#6
Yan Kuang, Fangfang Lu, Jianfeng Guo, Hong Xu, Qi Wang, Chaohuan Xu, Longjia Zeng, Suyi Yi
Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28701406/structure-and-functional-basis-for-an-ebna1-hexameric-ring-in-epstein-barr-virus-episome-maintenance
#7
Julianna S Deakyne, Kimberly Malecka, Troy E Messick, Paul M Lieberman
Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the x-ray crystal structure of an EBNA1 DNA binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher order EBNA1 complexes...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701309/arhgap18-protects-against-thoracic-aortic-aneurysm-formation-by-mitigating-the-synthetic-and-pro-inflammatory-smooth-muscle-cell-phenotype
#8
Renjing Liu, Lisa Lo, Angelina J Lay, Yang Zhao, Ka Ka Ting, Elizabeth N Robertson, Andrew G Sherrah, Sorour R Jarrah, Haibo Li, Zhaoxiong Zhou, Brett D Hambly, David R Richmond, Richmond W Jeremy, Paul G Bannon, Matthew A Vadas, Jennifer Gamble
Rationale: Thoracic aortic aneurysm (TAA) is a potentially lethal condition which can affect individuals of all ages. TAA may be complicated by the sudden onset of life threatening dissection or rupture. The underlying mechanisms leading to TAA formation, particularly in the non-syndromal idiopathic group of patients, are not well understood. Thus, identification of new genes and targets that are involved in TAA pathogenesis are required to help prevent and/or reverse the disease phenotype. Objective: Here we explore the role of ARHGAP18, a novel Rho GAP expressed by smooth muscle cells (SMC), in the pathogenesis of TAA...
July 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28691095/condensin-ii-is-anchored-by-tfiiic-and-h3k4me3-in-the-mammalian-genome-and-supports-the-expression-of-active-dense-gene-clusters
#9
Kobe C Yuen, Brian D Slaughter, Jennifer L Gerton
Structural maintenance of chromosome complexes, such as cohesin, have been implicated in a wide variety of chromatin-dependent functions such as genome organization, replication, and gene expression. How these complexes find their sites of association and affect local chromosomal processes is not well understood. We report that condensin II, a complex distinct from cohesin, physically interacts with TFIIIC, and they both colocalize at active gene promoters in the mouse and human genomes, facilitated by interaction between NCAPD3 and the epigenetic mark H3K4me3...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28683716/putative-enhancer-sites-in-the-bovine-genome-are-enriched-with-variants-affecting-complex-traits
#10
Min Wang, Timothy P Hancock, Iona M MacLeod, Jennie E Pryce, Benjamin G Cocks, Benjamin J Hayes
BACKGROUND: Enhancers are non-coding DNA sequences, which when they are bound by specific proteins increase the level of gene transcription. Enhancers activate unique gene expression patterns within cells of different types or under different conditions. Enhancers are key contributors to gene regulation, and causative variants that affect quantitative traits in humans and mice have been located in enhancer regions. However, in the bovine genome, enhancers as well as other regulatory elements are not yet well defined...
July 6, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28678843/kshv-encoded-orf59-modulates-histone-arginine-methylation-of-the-viral-genome-to-promote-viral-reactivation
#11
Roxanne C Strahan, Maria McDowell-Sargent, Timsy Uppal, Pravinkumar Purushothaman, Subhash C Verma
Kaposi's sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into 'open' chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28676122/genome-wide-search-for-zelda-like-chromatin-signatures-identifies-gaf-as-a-pioneer-factor-in-early-fly-development
#12
Arbel Moshe, Tommy Kaplan
BACKGROUND: The protein Zelda was shown to play a key role in early Drosophila development, binding thousands of promoters and enhancers prior to maternal-to-zygotic transition (MZT), and marking them for transcriptional activation. Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters. Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein...
July 4, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28664508/correlation-between-expression-of-recombinant-proteins-and-abundance-of-h3k4me3-on-the-enhancer-of-human-cytomegalovirus-major-immediate-early-promoter
#13
Benjamin P C Soo, Julian Tay, Shirelle Ng, Steven C L Ho, Yuansheng Yang, Sheng-Hao Chao
Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter...
June 29, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28663191/the-histone-methyltransferase-mll1-directs-macrophage-mediated-inflammation-in-wound-healing-and-is-altered-in-a-murine-model-of-obesity-and-type-2-diabetes
#14
Andrew Kimball, Amrita Joshi, William F Carson, Anna Boniakowski, Frank Davis, Matthew Schaller, Ronald Allen, Jennifer Bermick, Peter K Henke, Charles F Burant, Steve L Kunkel, Katherine A Gallagher
Macrophages are critical for the initiation and resolution of the inflammatory phase of wound repair. In diabetes, macrophages display a prolonged inflammatory phenotype in late wound healing. Recently, Mixed-Lineage Leukemia-1 (MLL1) has been shown to direct gene expression by regulating NFκB-mediated inflammatory gene transcription. Thus, we hypothesized that MLL1 influences macrophage-mediated inflammation in wound repair. We utilized a myeloid-specific Mll1 knockout(Mll1(f/f)Lyz2(Cre+) ) to determine the function of MLL1 in wound healing...
June 29, 2017: Diabetes
https://www.readbyqxmd.com/read/28651088/genetic-and-epigenetic-alterations-in-normal-and-sensitive-copd-diseased-human-bronchial-epithelial-cells-repeatedly-exposed-to-air-pollution-derived-pm2-5
#15
B Leclercq, A Platel, S Antherieu, L Y Alleman, E M Hardy, E Perdrix, N Grova, V Riffault, B M Appenzeller, M Happillon, F Nesslany, P Coddeville, J-M Lo-Guidice, G Garçon
Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface...
June 23, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28642444/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#16
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630052/infection-exposure-promotes-etv6-runx1-precursor-b-cell-leukemia-via-impaired-h3k4-demethylases
#17
Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Ines Gonzalez-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René M Linka, Marta Garcia-Suquia, María V Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begona Garcia-Cenador, Francisco Javier Garcia-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28620206/analysis-of-m%C3%A3-ller-glia-specific-genes-and-their-histone-modification-using-hes1-promoter-driven-egfp-expressing-mouse
#18
Kazuko Ueno, Toshiro Iwagawa, Genki Ochiai, Hideto Koso, Hiromitsu Nakauchi, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe
Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify Müller glia-specific molecular signatures during retinal development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive Müller glia and other EGFP-negative retinal cells from developing retinas and subjected them to RNA sequencing analysis. Gene expression pattern of EGFP-positive cell was similar to genes expressed in retinal progenitors, and they were downregulated in other cell lineages...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611454/integrated-analysis-and-transcript-abundance-modelling-of-h3k4me3-and-h3k27me3-in-developing-secondary-xylem
#19
Steven G Hussey, Mattheus T Loots, Karen van der Merwe, Eshchar Mizrachi, Alexander A Myburg
Despite the considerable contribution of xylem development (xylogenesis) to plant biomass accumulation, its epigenetic regulation is poorly understood. Furthermore, the relative contributions of histone modifications to transcriptional regulation is not well studied in plants. We investigated the biological relevance of H3K4me3 and H3K27me3 in secondary xylem development using ChIP-seq and their association with transcript levels among other histone modifications in woody and herbaceous models. In developing secondary xylem of the woody model Eucalyptus grandis, H3K4me3 and H3K27me3 genomic spans were distinctly associated with xylogenesis-related processes, with (late) lignification pathways enriched for putative bivalent domains, but not early secondary cell wall polysaccharide deposition...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609469/muscle-relevant-genes-marked-by-stable-h3k4me2-3-profiles-and-enriched-myod-binding-during-myogenic-differentiation
#20
Huanhuan Cui, Vikas Bansal, Marcel Grunert, Barbora Malecova, Alessandra Dall'Agnese, Lucia Latella, Sole Gatto, Tammy Ryan, Kerstin Schulz, Wei Chen, Cornelia Dorn, Pier Lorenzo Puri, Silke R Sperling
Post-translational modifications of histones play a key role in the regulation of gene expression during development and differentiation. Numerous studies have shown the dynamics of combinatorial regulation by transcription factors and histone modifications, in the sense that different combinations lead to distinct expression outcomes. Here, we investigated gene regulation by stable enrichment patterns of histone marks H3K4me2 and H3K4me3 in combination with the chromatin binding of the muscle tissue-specific transcription factor MyoD during myogenic differentiation of C2C12 cells...
2017: PloS One
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