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3D genomics

Xiaowen Lyu, Victor G Corces
No abstract text is available yet for this article.
December 4, 2018: Cell Research
Felix Fischbach, Julia Nedelcu, Patrizia Leopold, Jiangshan Zhan, Tim Clarner, Lara Nellessen, Christian Beißel, Yasemin van Heuvel, Anand Goswami, Joachim Weis, Bernd Denecke, Christoph Schmitz, Tanja Hochstrasser, Stella Nyamoya, Marion Victor, Cordian Beyer, Markus Kipp
Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions...
December 3, 2018: Glia
Akanksha Jaiswar, Deepti Varshney, Alok Adholeya, Pushplata Prasad
BACKGROUND: Environmental stress induced genetic polymorphisms have been suggested to arbitrate functional modifications influencing adaptations in microbes. The relationship between the genetic processes and concomitant functional adaptation can now be investigated at a genomic scale with the help of next generation sequencing (NGS) technologies. Using a NGS approach we identified genetic variations putatively underlying chromium tolerance in a strain of Aspergillus flavus isolated from a tannery sludge...
December 4, 2018: BMC Genomics
Agnieska Brazovskaja, Barbara Treutlein, J Gray Camp
Three-dimensional (3D) tissues grown in culture from human stem cells offer the incredible opportunity to analyze and manipulate human development, and to generate patient-specific models of disease. Methods to sequence DNA and RNA in single cells are being used to analyze these so-called 'organoid' systems in high-resolution. Single-cell transcriptomics has been used to quantitate the similarity of organoid cells to primary tissue counterparts in the brain, intestine, liver, and kidney, as well as identify cell-specific responses to environmental variables and disease conditions...
November 29, 2018: Current Opinion in Biotechnology
Farzane Kargar, Mojtaba Mortazavi, Amir Savardashtaki, Saman Hosseinkhani, Masoud Torkzadeh Mahani, Younes Ghasemi
To date, two Iranian luciferase genes from the Lampyris turkestanicus and Lampyroidea maculata have been carefully studied. Here, we report the cloning and characterization of the gene and protein of luciferase enzyme from the beetle of an Iranian lampyrid species, Calopteron terminale (Coleoptera-Lampyridae). In this study, a Calopteron terminale firefly was collected from the Yasouj area of Iran and its luciferase gene sequence was cloned and characterized. The genomic DNA length for this luciferase was the 1950 bp that combined of seven exons and separated by six introns...
November 28, 2018: International Journal of Biological Macromolecules
Mahdieh Jadaliha, Omid Gholamalamdari, Wei Tang, Yang Zhang, Ana Petracovici, Qinyu Hao, Aamira Tariq, Tae Gyoon Kim, Sarah E Holton, Deepak K Singh, Xiao Ling Li, Susan M Freier, Stefan Ambs, Rohit Bhargava, Ashish Lal, Supriya G Prasanth, Jian Ma, Kannanganattu V Prasanth
The human genome encodes thousands of long noncoding RNA (lncRNA) genes; the function of majority of them is poorly understood. Aberrant expression of a significant number of lncRNAs is observed in various diseases, including cancer. To gain insights into the role of lncRNAs in breast cancer progression, we performed genome-wide transcriptome analyses in an isogenic, triple negative breast cancer (TNBC/basal-like) progression cell lines using a 3D cell culture model. We identified significantly altered expression of 1853 lncRNAs, including ~500 natural antisense transcript (NATs) lncRNAs...
November 29, 2018: PLoS Genetics
Brandon M Butler, I Can Kazan, Avishek Kumar, S Banu Ozkan
The conformational dynamics of proteins is rarely used in methodologies used to predict the impact of genetic mutations due to the paucity of three-dimensional protein structures as compared to the vast number of available sequences. Until now a three-dimensional (3D) structure has been required to predict the conformational dynamics of a protein. We introduce an approach that estimates the conformational dynamics of a protein, without relying on structural information. This de novo approach utilizes coevolving residues identified from a multiple sequence alignment (MSA) using Potts models...
November 29, 2018: PLoS Computational Biology
Haishuang Lin, Qian Du, Qiang Li, Ou Wang, Zhanqi Wang, Kan Liu, Leonard Akert, Chi Zhang, Soonkyu Chung, Bin Duan, Yuguo Lei
Vascular smooth muscle cells (VSMCs) are of great value and are needed in large quantities for tissue engineering, drug screening, disease modeling and cell-based therapies. However, getting high quantity VSMCs remains a challenge. Here, we report a method for the scalable manufacturing of VSMCs from human pluripotent stem cells (hPSCs). hPSCs are expanded and differentiated into VSMCs in a three dimensional (3D) thermoreversible hydrogel. The hydrogel not only acts as a 3D scaffold for cells to grow, but also protects cells from hydrodynamic stresses in the culture vessel and prevents cells from excessive aggregation...
November 28, 2018: Biomaterials Science
Jose M Ayuso, Amani Gillette, Karina Lugo-Cintrón, Suehelay Acevedo-Acevedo, Ismael Gomez, Molly Morgan, Tiffany Heaster, Kari B Wisinski, Sean P Palecek, Melissa C Skala, David J Beebe
BACKGROUND: Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer. During DCIS, tumor cells remain inside the mammary duct, growing under a microenvironment characterized by hypoxia, nutrient starvation, and waste product accumulation; this harsh microenvironment promotes genomic instability and eventually cell invasion. However, there is a lack of biomarkers to predict what patients will transition to a more invasive tumor or how DCIS cells manage to survive in this harsh microenvironment...
October 25, 2018: EBioMedicine
John E Froberg, Stefan F Pinter, Andrea J Kriz, Teddy Jégu, Jeannie T Lee
The mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for how the 3D genome is organized. The Xi shows weakened topologically associated domains and is instead organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not precede Xist expression or Xi gene silencing...
November 27, 2018: Nature Communications
Axel Poulet, Ben Li, Tristan Dubos, Juan Carlos Rivera-Mulia, David M Gilbert, Zhaohui S Qin
Motivation: The replication timing (RT) program has been linked to many key biological processes including cell fate commitment, 3D chromatin organization and transcription regulation. Significant technology progress now allows to characterize the RT program in the entire human genome in a high-throughput and high-resolution fashion. These experiments suggest that RT changes dynamically during development in coordination with gene activity. Since RT is such a fundamental biological process, we believe that an effective quantitative profile of the local RT program from a diverse set of cell types in various developmental stages and lineages can provide crucial biological insights for a genomic locus...
November 22, 2018: Bioinformatics
Maria Giorgia Morselli, Monica Loiacono, Martina Colombo, Michele Mortarino, Gaia Cecilia Luvoni
To evaluate the ability of a 3D culture system in improving the nuclear and molecular competence of canine oocytes, barium alginate microcapsules were used for in vitro maturation (IVM) and the expression profile of one selected oocyte-secreted factor, the growth differentiation factor-9 (GDF-9) was analysed. In Experiment I, canine grade I cumulus-oocyte complexes (COCs) were in vitro matured in 3D microcapsules in a controlled atmosphere for 72 hr, and meiosis resumption rates were compared to those of oocytes cultured in traditional 2D microdrops of medium...
November 2018: Reproduction in Domestic Animals, Zuchthygiene
Hongqi Wang, Yan Yang, Jie Xu, Dekang Kong, Yi Li
To reveal the molecular mechanism at the level of regulation of proteins in Rhodococcus sp. BAP-1 induced by fluoranthene comparative proteomic analysis was performed on proteins extracted from fluoranthene-exposed cells on 1 d, 3 d, 6 d and 8 d compared with control cells using isobaric tags for relative and absolute quantization (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. As a result, we detected a total of 897 significantly differentially expressed proteins, including 30 shared proteins in four comparison clusters...
November 17, 2018: Ecotoxicology and Environmental Safety
Ha Youn Shin
BACKGROUND: Super-enhancers play critical roles in cell-type specific gene controls and human disease progression. CCCTC-binding factor (CTCF), a transcriptional repressor that insulates the expression of neighboring genes and is involved in chromatin interactions, is frequently present in the boundary regions of or within super-enhancers. However, the structural and functional roles of CTCF in regulating super-enhancers remain elusive. OBJECTIVE: To provide a comprehensive review describing the distinct chromatin features and functional roles of CTCF within super-enhancers...
November 19, 2018: Genes & Genomics
Xuelei Lai, Arnaud Stigliani, Gilles Vachon, Cristel Carles, Cezary Smaczniak, Chloe Zubieta, Kerstin Kaufmann, François Parcy
Transcription factors (TF) are key cellular components that control gene expression. They recognize specific DNA sequences, the TF binding sites (TFBS), and thus are targeted to specific regions of the genome where they can recruit transcriptional cofactors and/or chromatin regulators for fine-tuning spatiotemporal gene regulation. Therefore, the identification of TFBS in genomic sequences and their subsequent quantitative modeling is of crucial importance for understanding and predicting gene expression. Here, we review how TFBS can be determined experimentally, how the TFBS models can be constructed in silico, and how they can be optimized by taking into account features such as position interdependence within TFBSs, DNA shape and/or by introducing state-of-the-art computational algorithms such as deep learning methods...
November 14, 2018: Molecular Plant
Moritz Schaefer, Djork-Arné Clevert, Bertram Weiss, Andreas Steffen
Summary: sgRNAs targeting the same gene can significantly vary in terms of efficacy and specificity. PAVOOC (Prediction And Visualization of On- and Off-targets for CRISPR) is a web-based CRISPR sgRNA design tool that employs state of the art machine learning models to prioritize most effective candidate sgRNAs. In contrast to other tools, it maps sgRNAs to functional domains and protein structures and visualizes cut sites on corresponding protein crystal structures. Furthermore, PAVOOC supports homology-directed repair template generation for genome editing experiments and the visualization of the mutated amino acids in 3D...
November 16, 2018: Bioinformatics
Xianfeng Li, Leisheng Shi, Yan Wang, Jianing Zhong, Xiaolu Zhao, Huajing Teng, Xiaohui Shi, Haonan Yang, Shasha Ruan, MingKun Li, Zhong Sheng Sun, Qimin Zhan, Fengbiao Mao
Whole-exome and whole-genome sequencing have revealed millions of somatic mutations associated with different human cancers, and the vast majority of them are located outside of coding sequences, making it challenging to directly interpret their functional effects. With the rapid advances in high-throughput sequencing technologies, genome-scale long-range chromatin interactions were detected, and distal target genes of regulatory elements were determined using three-dimensional (3D) chromatin looping. Herein, we present OncoBase (http://www...
November 16, 2018: Nucleic Acids Research
M Aydın Akbudak, Ertugrul Filiz, Senem Uylas
Cysteine (Cys) is the first identified molecule in plant metabolism which includes both sulfur and nitrogen. It can be synthesized in three cellular compartments, containing chloroplast, cytoplasm and mitochondrion. The final step of cysteine biosynthesis is catalyzed by the O-acetylserine(thiol)lyase enzyme (OASTL, E.C. 4.2.99). In the present study, seven members of the OASTL gene family in the sorghum (Sorghum bicolor) genome were identified at a genome-wide scale and comparative bioinformatics analyses were performed between sorghum and Arabidopsis OASTLs...
November 15, 2018: Molecular Biology Reports
Elrashdy M Redwan, Abdullah A AlJaddawi, Vladimir N Uversky
Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems...
November 15, 2018: Cellular and Molecular Life Sciences: CMLS
Katherine A Easterling, Nicholi J Pitra, Rachel J Jones, Lauren G Lopes, Jenna R Aquino, Dong Zhang, Paul D Matthews, Hank W Bass
Hop ( Humulus lupulus L.) is an important crop worldwide, known as the main flavoring ingredient in beer. The diversifying brewing industry demands variation in flavors, superior process properties, and sustainable agronomics, which are the focus of advanced molecular breeding efforts in hops. Hop breeders have been limited in their ability to create strains with desirable traits, however, because of the unusual and unpredictable inheritance patterns and associated non-Mendelian genetic marker segregation. Cytogenetic analysis of meiotic chromosome behavior has also revealed conspicuous and prevalent occurrences of multiple, atypical, non-disomic chromosome complexes, including those involving autosomes in late prophase...
2018: Frontiers in Plant Science
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