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3D genomics

Laurence Tessier, Olivier Côté, Dorothee Bienzle
Background: Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. This study aimed to determine the utility of RNA-Seq to call gene sequence variants, and to identify sequence variants of potential relevance to the pathogenesis of asthma. Methods: RNA-Seq data were generated from endobronchial biopsies collected from six asthmatic and seven non-asthmatic horses before and after challenge (26 samples total)...
2018: PeerJ
Jie Li, Yindong Li, Songjian Zhang, Hongmei Ma, XiaoXiao Liu, Zhichao Liang, Wenzeng Zhang, Hongbo Jing, Yiwei Du, Yang Yang, Da Huo, Lijuan Chen, Quanyi Wang
Background: Subgenotype C4 of enterovirus 71 (EV71) is the predominant agent of Hand Foot and Mouth disease (HFMD) circulating in the mainland of China. For the first time, a subgenotype C2 of EV71 named SY30-2 was isolated from a HFMD case in Beijing, China. Since it is uncertain whether antibodies raised against subgenotype C4 of EV71 can protect C2 EV71, it is important to monitor and check the presence of cross-reactive antibodies against new EV71 subgenotypes. To find out the causes for the different NtAb, this study is to investigate the relationships between amino acid residue variations and cross-reactive antibodies against EV71 subgenotypes C2 and C4...
2018: Frontiers in Microbiology
Pierrick Moreau, Axel Cournac, Gianna Aurora Palumbo, Martial Marbouty, Shogofa Mortaza, Agnes Thierry, Stefano Cairo, Marc Lavigne, Romain Koszul, Christine Neuveut
Whether non-integrated viral DNAs distribute randomly or target specific positions within the higher-order architecture of mammalian genomes remains largely unknown. Here we use Hi-C and viral DNA capture (CHi-C) in primary human hepatocytes infected by either hepatitis B virus (HBV) or adenovirus type 5 (Ad5) virus to show that they adopt different strategies in their respective positioning at active chromatin. HBV contacts preferentially CpG islands (CGIs) enriched in Cfp1 a factor required for its transcription...
October 15, 2018: Nature Communications
Haifeng Wang, Xiaoshu Xu, Cindy M Nguyen, Yanxia Liu, Yuchen Gao, Xueqiu Lin, Timothy Daley, Nathan H Kipniss, Marie La Russa, Lei S Qi
Programmable control of spatial genome organization is a powerful approach for studying how nuclear structure affects gene regulation and cellular function. Here, we develop a versatile CRISPR-genome organization (CRISPR-GO) system that can efficiently control the spatial positioning of genomic loci relative to specific nuclear compartments, including the nuclear periphery, Cajal bodies, and promyelocytic leukemia (PML) bodies. CRISPR-GO is chemically inducible and reversible, enabling interrogation of real-time dynamics of chromatin interactions with nuclear compartments in living cells...
October 8, 2018: Cell
Daniel Schuetzmann, Carolin Walter, Boet van Riel, Sabrina Kruse, Thorsten König, Tabea Erdmann, Alexander Tönges, Eric Bindels, Andre Weilemann, Claudia Gebhard, Klaus Wethmar, Chiara Perrod, Julia Minderjahn, Michael Rehli, Ruud Delwel, Georg Lenz, Stefan Gröschel, Martin Dugas, Frank Rosenbauer
Epigenetic control of gene expression occurs within discrete spatial chromosomal units called topologically associating domains (TADs), but the exact spatial requirements of most genes are unknown; this is of particular interest for genes involved in cancer. We therefore applied high-resolution chromosomal conformation capture-sequencing to map the three-dimensional (3D) organization of the human locus encoding the key myeloid transcription factor PU.1 in healthy monocytes and acute myeloid leukemia (AML) cells...
October 12, 2018: Blood
Lokanadha R Gunupuru, Chanemougasoundharam Arunachalam, Keshav B Malla, Amal Kahla, Alexandre Perochon, Jianguang Jia, Ganesh Thapa, Fiona M Doohan
The mycotoxin deoxynivalenol (DON) serves as a plant disease virulence factor for the fungi Fusarium graminearum and F. culmorum during the development of Fusarium head blight (FHB) disease on wheat. A wheat cytochrome P450 gene from the subfamily CYP72A, TaCYP72A, was cloned from wheat cultivar CM82036. TaCYP72A was located on chromosome 3A with homeologs present on 3B and 3D of the wheat genome. Using gene expression studies, we showed that TaCYP72A variants were activated in wheat spikelets as an early response to F...
2018: PloS One
Mo Li, Zhibo Ma, Sharmila Roy, Sapna K Patel, Derrick C Lane, Carly R Duffy, Haini N Cai
The three-dimensional organization of the eukaryotic genome is important for its structure and function. Recent studies indicate that hierarchies of chromatin loops underlie important aspects of both genomic organization and gene regulation. Looping between insulator or boundary elements interferes with enhancer-promoter communications and limits the spread active or repressive organized chromatin. We have used the SF1 insulator in the Drosophila Antennapedia homeotic gene complex (ANT-C) as a model to study the mechanism and regulation of chromatin looping events...
October 11, 2018: Scientific Reports
M Aydın Akbudak, Ertugrul Filiz, Kubra Kontbay
Biotic and abiotic stresses negatively affect fitness, biomass production, and crop yield in plants. The dehydration-responsive element-binding proteins ( DREB ) are important transcription factors (TFs), and are induced by abiotic and biotic stresses. In this study, genome-wide identification, in silico sequence, and phylogenetic analyses and expression analyses of DREB2 genes under cadmium (Cd) and salt (NaCl) stresses in sorghum ( Sorghum bicolor , Sb ) were performed. Six putative SbDREB2 genes were identified in sorghum genome and all contained AP2 domain (PF00847)...
October 2018: 3 Biotech
Stefan Schoenfelder, Borbala Mifsud, Claire E Senner, Christopher D Todd, Stephanie Chrysanthou, Elodie Darbo, Myriam Hemberger, Miguel R Branco
The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes...
October 10, 2018: Nature Communications
Sungsik Kim, Amos Chungwon Lee, Han-Byoel Lee, Jinhyun Kim, Yushin Jung, Han Suk Ryu, Yongju Lee, Sangwook Bae, Minju Lee, Kyungmin Lee, Ryong Nam Kim, Woong-Yang Park, Wonshik Han, Sunghoon Kwon
Spatial mapping of genomic data to tissue context in a high-throughput and high-resolution manner has been challenging due to technical limitations. Here, we describe PHLI-seq, a novel approach that enables high-throughput isolation and genome-wide sequence analysis of single cells or small numbers of cells to construct genomic maps within cancer tissue in relation to the images or phenotypes of the cells. By applying PHLI-seq, we reveal the heterogeneity of breast cancer tissues at a high resolution and map the genomic landscape of the cells to their corresponding spatial locations and phenotypes in the 3D tumor mass...
October 8, 2018: Genome Biology
Clemens B Hug, Juan M Vaquerizas
The 3D structure of chromatin in the nucleus is important for the regulation of gene expression and the correct deployment of developmental programs. The differentiation of germ cells and early embryonic development (when the zygotic genome is activated and transcription is taking place for the first time) are accompanied by dramatic changes in gene expression and the epigenetic landscape. Recent studies used Hi-C to investigate the 3D chromatin organization during these developmental transitions, uncovering remarkable remodeling of the 3D genome...
October 3, 2018: Trends in Genetics: TIG
Kelli M Wilson, Lesley A Mathews-Griner, Tara Williamson, Rajarshi Guha, Lu Chen, Paul Shinn, Crystal McKnight, Sam Michael, Carleen Klumpp-Thomas, Zev A Binder, Marc Ferrer, Gary L Gallia, Craig J Thomas, Gregory J Riggins
Glioblastoma (GBM) is a lethal brain cancer with a median survival time of approximately 15 months following treatment. Common in vitro GBM models for drug screening are adherent and do not recapitulate the features of human GBM in vivo. Here we report the genomic characterization of nine patient-derived, spheroid GBM cell lines that recapitulate human GBM characteristics in orthotopic xenograft models. Genomic sequencing revealed that the spheroid lines contain alterations in GBM driver genes such as PTEN, CDKN2A, and NF1...
October 5, 2018: SLAS Technology
Yanli Wang, Fan Song, Bo Zhang, Lijun Zhang, Jie Xu, Da Kuang, Daofeng Li, Mayank N K Choudhary, Yun Li, Ming Hu, Ross Hardison, Ting Wang, Feng Yue
Here, we introduce the 3D Genome Browser, , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. We design a new binary data format for Hi-C data that reduces the file size by at least a magnitude and allows users to visualize chromatin interactions over millions of base pairs within seconds. Our browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure...
October 4, 2018: Genome Biology
Mudassar Ahmad, Xinhui Yan, Jianzhao Li, Qinsong Yang, Wajeeha Jamil, Yuanwen Teng, Songling Bai
BACKGROUND: NAC proteins contribute to diverse plant developmental processes as well as tolerances to biotic and abiotic stresses. The pear genome had been decoded and provided the basis for the genome-wide analysis to find the evolution, duplication, gene structures and predicted functions of PpNAC transcription factors. RESULTS: A total of 185 PpNAC genes were found in pear, of which 148 were mapped on chromosomes while 37 were on unanchored scaffolds. Phylogeny split the NAC genes into 6 clades (Group1- Group6) with their sub clades (~ subgroup A to subgroup H) and each group displayed common motifs with no/minor change...
October 3, 2018: BMC Plant Biology
Yao Fu, Kandice L Tessneer, Chuang Li, Patrick M Gaffney
Genome-wide association studies (GWAS) and fine mapping studies in autoimmune diseases have identified thousands of genetic variants, the majority of which are located in non-protein-coding enhancer regions. Enhancers function within the context of the three-dimensional (3D) genome to form long-range DNA looping events with target gene promoters that spatially and temporally regulate gene expression. Investigating the functional significance of GWAS variants in the context of the 3D genome is essential for mechanistic understanding of these variants and how they influence disease pathology by altering DNA looping between enhancers and the target gene promoters they regulate...
September 29, 2018: Arthritis Research & Therapy
Klaus Scherrer
The main purpose of this review is to recall for investigators - and in particular students -, some of the early data and concepts in molecular genetics and biology that are rarely cited in the current literature and are thus invariably overlooked. There is a growing tendency among editors and reviewers to consider that only data produced in the last 10-20 years or so are pertinent. However this is not the case. In exact science, sound data and lucid interpretation never become obsolete, and even if forgotten, will resurface sooner or later...
September 25, 2018: Experimental Cell Research
Mengnan He, Yan Li, Qianzi Tang, Diyan Li, Long Jin, Shilin Tian, Tiandong Che, Shen He, Lamei Deng, Guangliang Gao, Yiren Gu, Zhi Jiang, Xuewei Li, Mingzhou Li
The recently developed high-throughput chromatin conformation capture (Hi-C) technology enables us to explore the spatial architecture of genomes, which is increasingly considered an important regulator of gene expression. To investigate the changes in three-dimensional (3D) chromatin structure and its mediated gene expression during adipogenesis and myogenesis, we comprehensively mapped 3D chromatin organization for four cell types (3T3-L1 pre-adipocytes, 3T3-L1-D adipocytes, C2C12 myoblasts, and C2C12-D myotubes)...
2018: International Journal of Biological Sciences
Marc A Marti-Renom, Genevieve Almouzni, Wendy A Bickmore, Kerstin Bystricky, Giacomo Cavalli, Peter Fraser, Susan M Gasser, Luca Giorgetti, Edith Heard, Mario Nicodemi, Marcelo Nollmann, Modesto Orozco, Ana Pombo, Maria-Elena Torres-Padilla
Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate...
October 2018: Nature Genetics
Rafael Galupa, Edith Heard
In somatic nuclei of female therian mammals, the two X chromosomes display very different chromatin states: OneXis typically euchromatic and transcriptionally active, and the other is mostly silent and forms a cytologically detectable heterochromatic structure termed the Barr body. These differences, which arise during female development as a result of X-chromosome inactivation (XCI), have been the focus of research for many decades. Initial approaches to define the structure of the inactive X chromosome (Xi) and its relationship to gene expression mainly involved microscopy-based approaches...
September 26, 2018: Annual Review of Genetics
Gen Zheng, Alexandr A Kalinin, Ivo D Dinov, Walter Meixner, Shengtao Zhu, John W Wiley
Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco-2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco-2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium...
September 25, 2018: Journal of Cellular and Molecular Medicine
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