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Nucleic Acids Research

Yongbing Zhao, Jinyue Wang, Fang Liang, Yanxia Liu, Qi Wang, Hao Zhang, Meiye Jiang, Zhewen Zhang, Wenming Zhao, Yiming Bao, Zhang Zhang, Jiayan Wu, Yan W Asmann, Rujiao Li, Jingfa Xiao
Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, NucMap includes 798 experimental data from 477 samples across 15 species...
October 18, 2018: Nucleic Acids Research
Jesús Murga-Moreno, Marta Coronado-Zamora, Alejandra Bodelón, Antonio Barbadilla, Sònia Casillas
Since the migrations that led humans to colonize Earth, our species has faced frequent adaptive challenges that have left signatures in the landscape of genetic variation and that we can identify in our today's genomes. Here, we (i) perform an outlier approach on eight different population genetic statistics for 22 non-admixed human populations of the Phase III of the 1000 Genomes Project to detect selective sweeps at different historical ages, as well as events of recurrent positive selection in the human lineage; and (ii) create PopHumanScan, an online catalog that compiles and annotates all candidate regions under selection to facilitate their validation and thoroughly analysis...
October 18, 2018: Nucleic Acids Research
Syed Murtuza Baker, Connor Rogerson, Andrew Hayes, Andrew D Sharrocks, Magnus Rattray
ATAC-seq is a recently developed method to identify the areas of open chromatin in a cell. These regions usually correspond to active regulatory elements and their location profile is unique to a given cell type. When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells. This paper presents Scasat (single-cell ATAC-seq analysis tool), a complete pipeline to process scATAC-seq data with simple steps...
October 18, 2018: Nucleic Acids Research
Mehdi Moustaqil, Frank Fontaine, Jeroen Overman, Alex McCann, Timothy L Bailey, Paulina Rudolffi Soto, Akshay Bhumkar, Nichole Giles, Dominic J B Hunter, Yann Gambin, Mathias Francois, Emma Sierecki
During embryogenesis, vascular development relies on a handful of transcription factors that instruct cell fate in a distinct sub-population of the endothelium (1). The SOXF proteins that comprise SOX7, 17 and 18, are molecular switches modulating arterio-venous and lymphatic endothelial differentiation (2,3). Here, we show that, in the SOX-F family, only SOX18 has the ability to switch between a monomeric and a dimeric form. We characterized the SOX18 dimer in binding assays in vitro, and using a split-GFP reporter assay in a zebrafish model system in vivo...
October 18, 2018: Nucleic Acids Research
Hongwei Wang, Ludong Yang, Yan Wang, Leshi Chen, Huihui Li, Zhi Xie
RPFdb ( or is a public database for hosting, analyzing and visualizing ribosome profiling (ribo-seq) data. Since its initial release in 2015, the amount of new ribo-seq data has been considerably enlarged with the increasing popularity of ribo-seq technique. Here, we describe an updated version, RPFdb v2.0, which brings significant data expansion, feature improvements, and functionality optimization: (i) RPFdb v2.0 currently hosts 2884 ribo-seq datasets from 293 studies, covering 29 different species, in comparison with 777 datasets from 82 studies and 8 species in the previous version; (ii) A refined analysis pipeline with multi-step quality controls has been applied to improve the pre-processing and alignment of ribo-seq data; (iii) New functional modules have been added to provide actively translated open reading frames (ORFs) information for each ribo-seq data; (iv) More features have been made available to increase database usability...
October 18, 2018: Nucleic Acids Research
Jinyoung Park, Hongmin Lee, Namshik Han, Sojung Kwak, Han-Teo Lee, Jae-Hwan Kim, Keonjin Kang, Byoung Ha Youn, Jae-Hyun Yang, Hyeon-Ju Jeong, Jong-Sun Kang, Seon-Young Kim, Jeung-Whan Han, Hong-Duk Youn, Eun-Jung Cho
Constitutive heterochromatin undergoes a dynamic clustering and spatial reorganization during myogenic differentiation. However the detailed mechanisms and its role in cell differentiation remain largely elusive. Here, we report the identification of a muscle-specific long non-coding RNA, ChRO1, involved in constitutive heterochromatin reorganization. ChRO1 is induced during terminal differentiation of myoblasts, and is specifically localized to the chromocenters in myotubes. ChRO1 is required for efficient cell differentiation, with global impacts on gene expression...
October 18, 2018: Nucleic Acids Research
Teng Liu, Qiong Zhang, Jiankun Zhang, Chao Li, Ya-Ru Miao, Qian Lei, Qiubai Li, An-Yuan Guo
Extracellular vesicles (EVs), such as exosomes and microvesicles, acted as cell-to-cell communication vectors and potential biomarkers for diseases. microRNAs (miRNAs) are the most well studied molecules in EVs, thus a comprehensive investigation of miRNA expression profiles in EVs will be helpful to explore their functions and biomarkers. We curated 462 small RNA sequencing samples of EVs from 17 sources/diseases and constructed the EVmiRNA database ( to show the miRNA expression profiles...
October 18, 2018: Nucleic Acids Research
Penghui Bao, Kum-Loong Boon, Cindy L Will, Klaus Hartmuth, Reinhard Lührmann
The active 3D conformation of the spliceosome's catalytic U2/U6 RNA core is stabilised by a network of secondary and tertiary RNA interactions, but also depends on spliceosomal proteins for its formation. To determine the contribution towards splicing of specific RNA secondary and tertiary interactions in the U2/U6 RNA core, we introduced mutations in critical U6 nucleotides and tested their effect on splicing using a yeast in vitro U6 depletion/complementation system. Elimination of selected RNA tertiary interactions involving the U6 catalytic triad, or deletions of the bases of U6-U80 or U6-A59, had moderate to no effect on splicing, showing that the affected secondary and tertiary interactions are not required for splicing catalysis...
October 18, 2018: Nucleic Acids Research
Younghoon Jang, Aaron Broun, Chaochen Wang, Young-Kwon Park, Lenan Zhuang, Ji-Eun Lee, Eugene Froimchuk, Chengyu Liu, Kai Ge
Histone 3 lysine 4 (H3K4) methyltransferases MLL3 and MLL4 (MLL3/4) are required for enhancer activation during cell differentiation, though the mechanism is incompletely understood. We have attempted to address this issue by generating two mouse lines: one expressing H3.3K4M, a lysine-4-to-methionine (K4M) mutation of histone H3.3 that inhibits H3K4 methylation, and the other carrying conditional double knockout of MLL3/4 enzymatic SET domain. Expression of H3.3K4M in lineage-specific precursor cells depletes H3K4 methylation and impairs adipose tissue and muscle development...
October 18, 2018: Nucleic Acids Research
Yuji Masuda, Satoshi Mitsuyuki, Rie Kanao, Asami Hishiki, Hiroshi Hashimoto, Chikahide Masutani
DNA-damage tolerance protects cells via at least two sub-pathways regulated by proliferating cell nuclear antigen (PCNA) ubiquitination in eukaryotes: translesion DNA synthesis (TLS) and template switching (TS), which are stimulated by mono- and polyubiquitination, respectively. However, how cells choose between the two pathways remains unclear. The regulation of ubiquitin ligases catalyzing polyubiquitination, such as helicase-like transcription factor (HLTF), could play a role in the choice of pathway. Here, we demonstrate that the ligase activity of HLTF is stimulated by double-stranded DNA via HIRAN domain-dependent recruitment to stalled primer ends...
October 18, 2018: Nucleic Acids Research
Xing-Xing Dai, Jun-Chao Jiang, Qian-Qian Sha, Yu Jiang, Xiang-Hong Ou, Heng-Yu Fan
Meiotic maturation of mammalian oocytes depends on the temporally and spatially regulated cytoplasmic polyadenylation and translational activation of maternal mRNAs. Cytoplasmic polyadenylation is controlled by cis-elements in the 3'-UTRs of mRNAs including the polyadenylation signal (PAS), which is bound by the cleavage and polyadenylation specificity factor (CPSF) and the cytoplasmic polyadenylation element (CPE), which recruits CPE binding proteins. Using the 3'-UTRs of mouse Cpeb1, Btg4 and Cnot6l mRNAs, we deciphered the combinatorial code that controls developmental stage-specific translation during meiotic maturation: (i) translation of a maternal transcript at the germinal vesicle (GV) stage requires one or more PASs that locate far away from CPEs; (ii) PASs distal and proximal to the 3'-end of the transcripts are equally effective in mediating translation at the GV stage, as long as they are not close to the CPEs; (iii) Both translational repression at the GV stage and activation after germinal vesicle breakdown require at least one CPE adjacent to the PAS; (iv) The numbers and positions of CPEs in relation to PASs within the 3'-UTR of a given transcript determines its repression efficiency in GV oocytes...
October 18, 2018: Nucleic Acids Research
Constance M Smith, Terry F Hayamizu, Jacqueline H Finger, Susan M Bello, Ingeborg J McCright, Jingxia Xu, Richard M Baldarelli, Jonathan S Beal, Jeffrey Campbell, Lori E Corbani, Pete J Frost, Jill R Lewis, Sharon C Giannatto, Dave Miers, David R Shaw, James A Kadin, Joel E Richardson, Cynthia L Smith, Martin Ringwald
The mouse Gene Expression Database (GXD) is an extensive, well-curated community resource freely available at Covering all developmental stages, GXD includes data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments in wild-type and mutant mice. GXD's gene expression information is integrated with the other data in Mouse Genome Informatics and interconnected with other databases, placing these data in the larger biological and biomedical context...
October 17, 2018: Nucleic Acids Research
Huating Yuan, Min Yan, Guanxiong Zhang, Wei Liu, Chunyu Deng, Gaoming Liao, Liwen Xu, Tao Luo, Haoteng Yan, Zhilin Long, Aiai Shi, Tingting Zhao, Yun Xiao, Xia Li
High functional heterogeneity of cancer cells poses a major challenge for cancer research. Single-cell sequencing technology provides an unprecedented opportunity to decipher diverse functional states of cancer cells at single-cell resolution, and cancer scRNA-seq datasets have been largely accumulated. This emphasizes the urgent need to build a dedicated resource to decode the functional states of cancer single cells. Here, we developed CancerSEA ( or, the first dedicated database that aims to comprehensively explore distinct functional states of cancer cells at the single-cell level...
October 17, 2018: Nucleic Acids Research
Alexandra A Kuznetsova, Anna G Matveeva, Alexander D Milov, Yuri N Vorobjev, Sergei A Dzuba, Olga S Fedorova, Nikita A Kuznetsov
Human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5' side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Here, to examine the mechanism of broad substrate specificity of APE1, we performed pulsed electron-electron double resonance (PELDOR) spectroscopy and pre-steady-state kinetic analysis with Förster resonance energy transfer (FRET) detection of DNA conformational changes during DNA binding and lesion recognition...
October 17, 2018: Nucleic Acids Research
Henriette Franz, Alejandro Villarreal, Stefanie Heidrich, Pavankumar Videm, Fabian Kilpert, Ivan Mestres, Federico Calegari, Rolf Backofen, Thomas Manke, Tanja Vogel
Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatio-temporal activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer identity in early progenitors...
October 17, 2018: Nucleic Acids Research
Lina Ma, Jiabao Cao, Lin Liu, Qiang Du, Zhao Li, Dong Zou, Vladimir B Bajic, Zhang Zhang
Long non-coding RNAs (lncRNAs) have significant functions in a wide range of important biological processes. Although the number of known human lncRNAs has dramatically increased, they are poorly annotated, posing great challenges for better understanding their functional significance and elucidating their complex functioning molecular mechanisms. Here, we present LncBook (, a curated knowledgebase of human lncRNAs that features a comprehensive collection of human lncRNAs and systematic curation of lncRNAs by multi-omics data integration, functional annotation and disease association...
October 17, 2018: Nucleic Acids Research
Jianbo Tian, Zhihua Wang, Shufang Mei, Nan Yang, Yang Yang, Juntao Ke, Ying Zhu, Yajie Gong, Danyi Zou, Xiating Peng, Xiaoyang Wang, Hao Wan, Rong Zhong, Jiang Chang, Jing Gong, Leng Han, Xiaoping Miao
Alternative splicing (AS) is a widespread process that increases structural transcript variation and proteome diversity. Aberrant splicing patterns are frequently observed in cancer initiation, progress, prognosis and therapy. Increasing evidence has demonstrated that AS events could undergo modulation by genetic variants. The identification of splicing quantitative trait loci (sQTLs), genetic variants that affect AS events, might represent an important step toward fully understanding the contribution of genetic variants in disease development...
October 17, 2018: Nucleic Acids Research
John Rivera, Soile V E Keränen, Steven M Gallo, Marc S Halfon
The REDfly database provides a comprehensive curation of experimentally-validated Drosophila transcriptional cis-regulatory elements and includes information on DNA sequence, experimental evidence, patterns of regulated gene expression, and more. Now in its thirteenth year, REDfly has grown to over 23 000 records of tested reporter gene constructs and 2200 tested transcription factor binding sites. Recent developments include the start of curation of predicted cis-regulatory modules in addition to experimentally-verified ones, improved search and filtering, and increased interaction with the authors of curated papers...
October 17, 2018: Nucleic Acids Research
Sihyung Park, Seung Hyun Ahn, Eun Sol Cho, You Kyung Cho, Eun-Sook Jang, Sung Wook Chi
High-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP, also called CLIP-Seq) has been used to map global RNA-protein interactions. However, a critical caveat of HITS-CLIP results is that they contain non-linear background noise-different extent of non-specific interactions caused by individual transcript abundance-that has been inconsiderately normalized, resulting in sacrifice of sensitivity. To properly deconvolute RNA-protein interactions, we have implemented CLIPick, a flexible peak calling pipeline for analyzing HITS-CLIP data, which statistically determines the signal-to-noise ratio for each transcript based on the expression-dependent background simulation...
October 17, 2018: Nucleic Acids Research
Jan Silhan, Qiyuan Zhao, Evzen Boura, Hellen Thomson, Andreas Förster, Christoph M Tang, Paul S Freemont, Geoff S Baldwin
NExo is an enzyme from Neisseria meningitidis that is specialized in the removal of the 3'-phosphate and other 3'-lesions, which are potential blocks for DNA repair. NExo is a highly active DNA 3'-phosphatase, and although it is from the class II AP family it lacks AP endonuclease activity. In contrast, the NExo homologue NApe, lacks 3'-phosphatase activity but is an efficient AP endonuclease. These enzymes act together to protect the meningococcus from DNA damage arising mainly from oxidative stress and spontaneous base loss...
October 17, 2018: Nucleic Acids Research
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