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Designer chromatin

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https://www.readbyqxmd.com/read/28638438/real-time-monitoring-of-ptahmgb-activity-in-poplar-transactivation-assays
#1
José M Ramos-Sánchez, Paolo M Triozzi, Alicia Moreno-Cortés, Daniel Conde, Mariano Perales, Isabel Allona
BACKGROUND: Precise control of gene expression is essential to synchronize plant development with the environment. In perennial plants, transcriptional regulation remains poorly understood, mainly due to the long time required to perform functional studies. Transcriptional reporters based on luciferase have been useful to study circadian and diurnal regulation of gene expression, both by transcription factors and chromatin remodelers. The high mobility group proteins are considered transcriptional chaperones that also modify the chromatin architecture...
2017: Plant Methods
https://www.readbyqxmd.com/read/28635365/nucleosomal-organization-and-dna-base-composition-patterns
#2
Alicia García, Sara González, Francisco Antequera
Nucleosomes are the basic units of chromatin. They compact the genome inside the nucleus and regulate the access of proteins to DNA. In the yeast genome, most nucleosomes occupy well-defined positions, which are maintained under many different physiological situations and genetic backgrounds. Although several short sequence elements have been described that favour or reduce the affinity between histones and DNA, the extent to which the DNA sequence affects nucleosome positioning in the genomic context remains unclear...
June 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28626364/ex-vivo-generation-of-genetically-modified-macrophages-from-human-induced-pluripotent-stem-cells
#3
Mania Ackermann, Alexandra Kuhn, Jessica Kunkiel, Sylvia Merkert, Ulrich Martin, Thomas Moritz, Nico Lachmann
BACKGROUND: Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have the capacity to differentiate towards all three germ layers and have been highlighted as an attractive cell source for the field of regenerative medicine. Thus, stable expression of therapeutic transgenes in iPSCs, as well as thereof derived progeny of hematopoietic lineage, may lay the foundation for innovative cell replacement therapies. METHODS: We have utilized human iPSC lines genetically modified by lentiviral vector technology or targeted integration of reporter genes to evaluate transgene expression during hematopoietic specification and differentiation towards macrophages...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28625518/histone-chaperone-asf1a-predicts-poor-outcomes-for-patients-with-gastrointestinal-cancer-and-drives-cancer-progression-by-stimulating-transcription-of-%C3%AE-catenin-target-genes
#4
Xiuming Liang, Xiaotian Yuan, Jingya Yu, Yujiao Wu, Kailin Li, Chao Sun, Shuyan Li, Li Shen, Feng Kong, Jihui Jia, Magnus Björkholm, Dawei Xu
Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3-H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28624199/engineering-next-generation-bet-independent-mlv-vectors-for-safer-gene-therapy
#5
Sara El Ashkar, Dominique Van Looveren, Franziska Schenk, Lenard S Vranckx, Jonas Demeulemeester, Jan De Rijck, Zeger Debyser, Ute Modlich, Rik Gijsbers
Retroviral vectors have shown their curative potential in clinical trials correcting monogenetic disorders. However, therapeutic benefits were compromised due to vector-induced dysregulation of cellular genes and leukemia development in a subset of patients. Bromodomain and extraterminal domain (BET) proteins act as cellular cofactors that tether the murine leukemia virus (MLV) pre-integration complex to host chromatin via interaction with the MLV integrase (IN) and thereby define the typical gammaretroviral integration distribution...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620032/a-moving-target-structure-and-disorder-in-pursuit-of-myc-inhibitors
#6
REVIEW
Richard Bayliss, Selena G Burgess, Eoin Leen, Mark W Richards
The Myc proteins comprise a family of ubiquitous regulators of gene expression implicated in over half of all human cancers. They interact with a large number of other proteins, such as transcription factors, chromatin-modifying enzymes and kinases. Remarkably, few of these interactions have been characterized structurally. This is at least in part due to the intrinsically disordered nature of Myc proteins, which adopt a defined conformation only in the presence of binding partners. Owing to this behaviour, crystallographic studies on Myc proteins have been limited to short fragments in complex with other proteins...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28609787/molecular-structures-guide-the-engineering-of-chromatin
#7
Stefan J Tekel, Karmella A Haynes
Chromatin is a system of proteins, RNA, and DNA that interact with each other to organize and regulate genetic information within eukaryotic nuclei. Chromatin proteins carry out essential functions: packing DNA during cell division, partitioning DNA into sub-regions within the nucleus, and controlling levels of gene expression. There is a growing interest in manipulating chromatin dynamics for applications in medicine and agriculture. Progress in this area requires the identification of design rules for the chromatin system...
June 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28606761/inhibition-of-bromodomain-containing-protein-9-for-the-prevention-of-epigenetically-defined-drug-resistance
#8
Terry D Crawford, Steffan Vartanian, Alexandre Côté, Steve Bellon, Martin Duplessis, E Megan Flynn, Michael Hewitt, Hon-Ren Huang, James R Kiefer, Jeremy Murray, Christopher G Nasveschuk, Eneida Pardo, F Anthony Romero, Peter Sandy, Yong Tang, Alexander M Taylor, Vickie Tsui, Jian Wang, Shumei Wang, Laura Zawadzke, Brian K Albrecht, Steven R Magnuson, Andrea G Cochran, David Stokoe
Bromodomain-containing protein 9 (BRD9), an epigenetic "reader" of acetylated lysines on post-translationally modified histone proteins, is upregulated in multiple cancer cell lines. To assess the functional role of BRD9 in cancer cell lines, we identified a small-molecule inhibitor of the BRD9 bromodomain. Starting from a pyrrolopyridone lead, we used structure-based drug design to identify a potent and highly selective in vitro tool compound 11, (GNE-375). While this compound showed minimal effects in cell viability or gene expression assays, it showed remarkable potency in preventing the emergence of a drug tolerant population in EGFR mutant PC9 cells treated with EGFR inhibitors...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28605403/power-and-sample-size-calculations-for-high-throughput-sequencing-based-experiments
#9
Chung-I Li, David C Samuels, Ying-Yong Zhao, Yu Shyr, Yan Guo
Power/sample size (power) analysis estimates the likelihood of successfully finding the statistical significance in a data set. There has been a growing recognition of the importance of power analysis in the proper design of experiments. Power analysis is complex, yet necessary for the success of large studies. It is important to design a study that produces statistically accurate and reliable results. Power computation methods have been well established for both microarray-based gene expression studies and genotyping microarray-based genome-wide association studies...
June 9, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28595940/glabridin-triggers-over-expression-of-mca1-and-nuc1-genes-in-candida-glabrata-is-it-an-apoptosis-inducer
#10
M Moazeni, M T Hedayati, M Nabili, S J Mousavi, A Abdollahi Gohar, S Gholami
The growing trends of emergence of antifungal-resistant Candida strains has recently been inspired the researchers to design new antifungal agents with novel mechanisms of action. Glabridin is an originally natural substrate with multiple biological activities which propose it as a novel anticancer, antimicrobial and antifungal agent. In the present study, the antifungal effect of glabridin against Candida glabrata isolates and its possible mechanism of action were investigated. The minimum inhibitory concentrations (MIC) for glabridin against fluconazole-resistant and fluconazole-SDD strains of C...
June 5, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28589190/cholesteric-liquid-crystals-in-living-matter
#11
REVIEW
Michel Mitov
Liquid crystals play an important role in biology because the combination of order and mobility is a basic requirement for self-organisation and structure formation in living systems. Cholesteric liquid crystals are omnipresent in living matter under both in vivo and in vitro conditions and address the major types of molecules essential to life. In the animal and plant kingdoms, the cholesteric structure is a recurring design, suggesting a convergent evolution to an optimised left-handed helix. Herein, we review the recent advances in the cholesteric organisation of DNA, chromatin, chitin, cellulose, collagen, viruses, silk and cholesterol ester deposition in atherosclerosis...
June 14, 2017: Soft Matter
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#12
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583311/next-generation-sequencing-of-nonmuscle-invasive-bladder-cancer-reveals-potential-biomarkers-and-rational-therapeutic-targets
#13
Eugene J Pietzak, Aditya Bagrodia, Eugene K Cha, Esther N Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E Rosenberg, Dean F Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B Solit, Bernard H Bochner
BACKGROUND: Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. OBJECTIVE: To identify genetic alterations with potential clinical implications in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory...
June 2, 2017: European Urology
https://www.readbyqxmd.com/read/28578698/dictyexpress-a-web-based-platform-for-sequence-data-management-and-analytics-in-dictyostelium-and-beyond
#14
Miha Stajdohar, Rafael D Rosengarten, Janez Kokosar, Luka Jeran, Domen Blenkus, Gad Shaulsky, Blaz Zupan
BACKGROUND: Dictyostelium discoideum, a soil-dwelling social amoeba, is a model for the study of numerous biological processes. Research in the field has benefited mightily from the adoption of next-generation sequencing for genomics and transcriptomics. Dictyostelium biologists now face the widespread challenges of analyzing and exploring high dimensional data sets to generate hypotheses and discovering novel insights. RESULTS: We present dictyExpress (2.0), a web application designed for exploratory analysis of gene expression data, as well as data from related experiments such as Chromatin Immunoprecipitation sequencing (ChIP-Seq)...
June 2, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28573110/nocardia-cyriacigeogica-from-bovine-mastitis-induced-in-vitro-apoptosis-of-bovine-mammary-epithelial-cells-via-activation-of-mitochondrial-caspase-pathway
#15
Wei Chen, Yongxia Liu, Limei Zhang, Xiaolong Gu, Gang Liu, Muhammad Shahid, Jian Gao, Tariq Ali, Bo Han
Nocardia is one of the causing agents of bovine mastitis and increasing prevalence of nocardial mastitis in shape of serious outbreaks has been reported from many countries. However, the mechanisms by which this pathogen damages the bovine mammary epithelial cells (bMECs) is not yet studied. Therefore, this study was designed with the aim to evaluate the apoptotic effects elicited by Nocardia and to investigate the pathway by which the Nocardia induce apoptosis in bMECs. Clinical Nocardia cyriacigeorgica strain from bovine mastitis was used to infect the bMECs for different time intervals, viz...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28567111/cytomorphologic-features-distinguishing-bethesda-category-iv-thyroid-lesions-from-parathyroid
#16
Simon Sung, Anjali Saqi, Elizabeth M Margolskee, John P Crapanzano
BACKGROUND: Thyroid follicular cells share similar cytomorphological features with parathyroid. Without a clinical suspicion, the distinction between a thyroid neoplasm and an intrathyroidal parathyroid can be challenging. The aim of this study was to assess the distinguishing cytomorphological features of parathyroid (including intrathyroidal) and Bethesda category IV (Beth-IV) thyroid follicular lesions, which carry a 15%-30% risk of malignancy and are often followed up with surgical resection...
2017: CytoJournal
https://www.readbyqxmd.com/read/28551748/anatomy-and-cell-biology-of-autism-spectrum-disorder-lessons-from-human-genetics
#17
Kristel T E Kleijer, Guillaume Huguet, Julie Tastet, Thomas Bourgeron, J P H Burbach
Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for which clues towards molecular and cellular pathogenesis were uncovered by genetic identification of susceptibility genes. Currently several hundreds of risk genes have been assigned, with a recurrence below 1% in the ASD population...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28548932/lncrna-tincr-attenuates-cardiac-hypertrophy-by-epigenetic-silencing-of-camkii
#18
Mingjing Shao, Guangdong Chen, Fengli Lv, Yanyan Liu, Hongjun Tian, Ran Tao, Ronghuan Jiang, Wei Zhang, Chuanjun Zhuo
In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28541304/digital-logic-circuits-in-yeast-with-crispr-dcas9-nor-gates
#19
Miles W Gander, Justin D Vrana, William E Voje, James M Carothers, Eric Klavins
Natural genetic circuits enable cells to make sophisticated digital decisions. Building equally complex synthetic circuits in eukaryotes remains difficult, however, because commonly used components leak transcriptionally, do not arbitrarily interconnect or do not have digital responses. Here, we designed dCas9-Mxi1-based NOR gates in Saccharomyces cerevisiae that allow arbitrary connectivity and large genetic circuits. Because we used the chromatin remodeller Mxi1, our gates showed minimal leak and digital responses...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#20
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
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