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3d genome

Amélie Bonnet-Garnier, Kiên Kiêu, Tiphaine Aguirre-Lavin, Krisztina Tar, Pierre Flores, Zichuan Liu, Nathalie Peynot, Martine Chebrout, András Dinnyés, Véronique Duranthon, Nathalie Beaujean
Changes to the spatial organization of specific chromatin domains such as constitutive heterochromatin have been studied extensively in somatic cells. During early embryonic development, drastic epigenetic reprogramming of both the maternal and paternal genomes, followed by chromatin remodeling at the time of embryonic genome activation (EGA), have been observed in the mouse. Very few studies have been performed in other mammalian species (human, bovine, or rabbit) and the data are far from complete. During this work, we studied the three-dimensional organization of pericentromeric regions during the preimplantation period in the rabbit using specific techniques (3D-FISH) and tools (semi-automated image analysis)...
April 18, 2018: Chromosoma
Simona Bianco, Darío G Lupiáñez, Andrea M Chiariello, Carlo Annunziatella, Katerina Kraft, Robert Schöpflin, Lars Wittler, Guillaume Andrey, Martin Vingron, Ana Pombo, Stefan Mundlos, Mario Nicodemi
Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and cause disease. However, the prediction of such effects remains a challenge. Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts...
April 16, 2018: Nature Genetics
Bo Wang, Jing Li, Xi Cheng, Qiao Zhou, Jingxu Yang, Menghuan Zhang, Haifeng Chen, Jing Li
Identifying deleterious mutations remains a challenge in cancer genome sequencing projects, reflecting the vast number of candidate mutations per tumour and the existence of interpatient heterogeneity. Based on a 3D protein interaction network profiled via large-scale cross-linking mass spectrometry, we propose a weighted average formula involving the combination of three types of information into a 'meta-score'. We assume that a single amino acid polymorphism (SAP) may have a deleterious effect if the mutation rarely occurs naturally during evolution, if it inhibits binding between a pair of interacting proteins when located at their interface, or if it plays an important role in a protein interaction (PPI) network...
April 16, 2018: Scientific Reports
Luyang Sun, Ruofan Yu, Weiwei Dang
Chromatin 3D structure is highly dynamic and associated with many biological processes, such as cell cycle progression, cellular differentiation, cell fate reprogramming, cancer development, cellular senescence, and aging. Recently, by using chromosome conformation capture technologies, tremendous findings have been reported about the dynamics of genome architecture, their associated proteins, and the underlying mechanisms involved in regulating chromatin spatial organization and gene expression. Cellular senescence and aging, which involve multiple cellular and molecular functional declines, also undergo significant chromatin structural changes, including alternations of heterochromatin and disruption of higher-order chromatin structure...
April 16, 2018: Genes
Peter J Skene, Jorja G Henikoff, Steven Henikoff
Cleavage under targets and release using nuclease (CUT&RUN) is an epigenomic profiling strategy in which antibody-targeted controlled cleavage by micrococcal nuclease releases specific protein-DNA complexes into the supernatant for paired-end DNA sequencing. As only the targeted fragments enter into solution, and the vast majority of DNA is left behind, CUT&RUN has exceptionally low background levels. CUT&RUN outperforms the most widely used chromatin immunoprecipitation (ChIP) protocols in resolution, signal-to-noise ratio and depth of sequencing required...
May 2018: Nature Protocols
I V Sharakhov, S M Bondarenko, G N Artemov, A V Onufriev
Chromosomes are intricately folded and packaged in the cell nucleus and interact with the nuclear envelope. This complex nuclear architecture has a profound effect on how the genome works and how the cells function. The main goal of review is to highlight recent studies on the effect of chromosome-nuclear envelope interactions on chromatin folding and function in the nucleus. The data obtained suggest that chromosome-nuclear envelope attachments are important for the organization of nuclear architecture in various organisms...
April 2018: Biochemistry. Biokhimii︠a︡
S V Razin
This issue of Biochemistry (Moscow) is devoted to the cell nucleus and mechanisms of transcription regulation. Over the years, biochemical processes in the cell nucleus have been studied in isolation, outside the context of their spatial organization. Now it is clear that segregation of functional processes within a compartmentalized cell nucleus is very important for the implementation of basic genetic processes. The functional compartmentalization of the cell nucleus is closely related to the spatial organization of the genome, which in turn plays a key role in the operation of epigenetic mechanisms...
April 2018: Biochemistry. Biokhimii︠a︡
Masae Ohno, David G Priest, Yuichi Taniguchi
Nucleosomes are the unitary structures of chromosome folding, and their arrangements are intimately coupled to the regulation of genome activities. Conventionally, structural analyses using electron microscopy and X-ray crystallography have been used to study such spatial nucleosome arrangements. In contrast, recent improvements in the resolution of sequencing-based methods allowed investigation of nucleosome arrangements separately at each genomic locus, enabling exploration of gene-dependent regulation mechanisms...
April 6, 2018: Biochemical Society Transactions
Nan Hua, Harianto Tjong, Hanjun Shin, Ke Gong, Xianghong Jasmine Zhou, Frank Alber
Chromosome conformation capture technologies such as Hi-C are widely used to investigate the spatial organization of genomes. Because genome structures can vary considerably between individual cells of a population, interpreting ensemble-averaged Hi-C data can be challenging, in particular for long-range and interchromosomal interactions. We pioneered a probabilistic approach for the generation of a population of distinct diploid 3D genome structures consistent with all the chromatin-chromatin interaction probabilities from Hi-C experiments...
May 2018: Nature Protocols
Yasuo Ouchi, Ashwini Patil, Yusuke Tamura, Hiroshi Nishimasu, Aina Negishi, Sudip Kumar Paul, Naoki Takemura, Takeshi Satoh, Yasumasa Kimura, Makoto Kurachi, Osamu Nureki, Kenta Nakai, Hiroshi Kiyono, Satoshi Uematsu
Immunotherapies have led to the successful development of novel therapies for cancer. However, there is increasing concern regarding the adverse effects caused by non-tumor-specific immune responses. Here, we report an effective strategy to generate high-avidity tumor-antigen-specific CTLs, using Cas9/single-guide RNA (sgRNA) ribonucleoprotein (RNP) delivery. As a proof-of-principle demonstration, we selected the gp100 melanoma-associated tumor antigen, and cloned the gp100-specific high-avidity TCR from gp100-immunized mice...
April 3, 2018: International Immunology
Sae Young Jin, Hyung Yell Choi, Han Sol Kim, Yong-Tae Jung
Although human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, hA3G)-mediated deamination is the major mechanism used to restrict the infectivity of a broad range of retroviruses, it is unclear whether porcine endogenous retrovirus (PERV) is affected by hA3G or porcine A3F (poA3F). To determine whether DNA deamination is required for hA3G- and poA3F-dependent inhibition of PERV transmission, we developed VSV-pseudotype PERV-B expressing hA3G, mutant hA3G-E67Q (encapsidation and RNA binding activity-deficient), mutant hA3G-E259Q (deaminase-deficient), or poA3F...
April 2, 2018: Archives of Virology
Margaret J Grant, Matthew S Loftus, Aiola P Stoja, Dean H Kedes, M Mitchell Smith
By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and crystallographic studies, there is little information addressing the 3D structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi's sarcoma-associated herpesvirus (KSHV)...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Javier Delgado Blanco, Leandro Radusky, Héctor Climente-González, Luis Serrano
The speed at which new genomes are being sequenced highlights the need for genome-wide methods capable of predicting protein-DNA interactions. Here, we present PADA1, a generic algorithm that accurately models structural complexes and predicts the DNA-binding regions of resolved protein structures. PADA1 relies on a library of protein and double-stranded DNA fragment pairs obtained from a training set of 2103 DNA-protein complexes. It includes a fast statistical force field computed from atom-atom distances, to evaluate and filter the 3D docking models...
March 28, 2018: Nucleic Acids Research
Jitendra Kumar Verma, Vijay Wardhan, Deepali Singh, Subhra Chakraborty, Niranjan Chakraborty
Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa , Zea mays , Sorghum bicolor , Cicer arietinum , and Vitis vinifera , and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii , Physcomitrella patens , and Amborella trichopoda , revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively...
March 28, 2018: Genes
Shamseldeen Eltaher, Ahmed Sallam, Vikas Belamkar, Hamdy A Emara, Ahmed A Nower, Khaled F M Salem, Jesse Poland, Peter S Baenziger
The availability of information on the genetic diversity and population structure in wheat ( Triticum aestivum L.) breeding lines will help wheat breeders to better use their genetic resources and manage genetic variation in their breeding program. The recent advances in sequencing technology provide the opportunity to identify tens or hundreds of thousands of single nucleotide polymorphism (SNPs) in large genome species (e.g., wheat). These SNPs can be utilized for understanding genetic diversity and performing genome wide association studies (GWAS) for complex traits...
2018: Frontiers in Genetics
Salvatore Loguercio, E Mauricio Barajas-Mora, Han-Yu Shih, Michael S Krangel, Ann J Feeney
CCCTC-binding factor (CTCF) is largely responsible for the 3D architecture of the genome, in concert with the action of cohesin, through the creation of long-range chromatin loops. Cohesin is hypothesized to be the main driver of these long-range chromatin interactions by the process of loop extrusion. Here, we performed ChIP-seq for CTCF and cohesin in two stages each of T and B cell differentiation and examined the binding pattern in all six antigen receptor (AgR) loci in these lymphocyte progenitors and in mature T and B cells, ES cells, and fibroblasts...
2018: Frontiers in Immunology
Tszshan Ma, Long Chen, Maoxiang Shi, Jing Niu, Xu Zhang, Xusan Yang, Karl Zhanghao, Miaoyan Wang, Peng Xi, Dayong Jin, Michael Zhang, Juntao Gao
To investigate three-dimensional (3D) genome organization in prokaryotic and eukaryotic cells, three main strategies are employed, namely nuclear proximity ligation-based methods, imaging tools (such as fluorescence in situ hybridization (FISH) and its derivatives), and computational/visualization methods. Proximity ligation-based methods are based on digestion and re-ligation of physically proximal cross-linked chromatin fragments accompanied by massively parallel DNA sequencing to measure the relative spatial proximity between genomic loci...
March 26, 2018: Cell Biology and Toxicology
Yuan Quan, Meng-Yuan Liu, Ye-Mao Liu, Li-Da Zhu, Yu-Shan Wu, Zhi-Hui Luo, Xiu-Zhen Zhang, Shi-Zhong Xu, Qing-Yong Yang, Hong-Yu Zhang
Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most diseases are not caused by a single pathogenic factor, but by multiple disease genes, in particular, interacting disease genes. Thus, it is reasonable to consider that targeting epistatic disease genes may enhance the therapeutic effects of combinatorial drugs...
March 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shibao Wang, Yinghui Huang, Xupeng Mu, Tianyang Qi, Sha Qiao, Zhenxia Lu, Hongjun Li
The present study aimed to explore the relationship between DNA methylation and breast cancer under different cell culture conditions. MCF‑7 breast cancer cells were cultured in two‑dimensional (2D), three‑dimensional (3D) and orthotopic transplantation (Ti) adhesion substrates. Principal component analysis (PCA) was used for global visualization of these three samples. The methylation status of CpG sites was examined by unsupervised clustering analysis. Scatter plots and histograms were constructed from the mean β‑values from 3D vs...
March 14, 2018: Molecular Medicine Reports
Rodrigo G Arzate-Mejía, Félix Recillas-Targa, Victor G Corces
CTCF is a highly conserved zinc-finger DNA-binding protein that mediates interactions between distant sequences in the genome. As a consequence, CTCF regulates enhancer-promoter interactions and contributes to the three-dimensional organization of the genome. Recent studies indicate that CTCF is developmentally regulated, suggesting that it plays a role in cell type-specific genome organization. Here, we review these studies and discuss how CTCF functions during the development of various cell and tissue types, ranging from embryonic stem cells and gametes, to neural, muscle and cardiac cells...
March 22, 2018: Development
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