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Genetic variation across and within individuals Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-28 Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin, Kristin G. Ardlie, Niall Lennon, Pradeep Natarajan
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AIRE targets poised promoters enriched for Z-DNA Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-27 Kirsty Minton
A paper in Nature reports a ‘Z-DNA-anchored’ model for the target specificity of the transcription factor AIRE, involving promoter poising at double-strand breaks.
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Building a catalogue of short tandem repeats in diverse populations Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-27 Ning Xie
Reflecting on the importance of short tandem repeats (STRs) in population genetics, Ning Xie highlights a 2023 publication that characterized genome-wide STR variation in global human genomes to expand our understanding of STR genetic diversity within and across populations.
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Protein-altering variants at copy number-variable regions influence diverse human phenotypes Nat. Genet. (IF 30.8) Pub Date : 2024-03-28 Margaux L. A. Hujoel, Robert E. Handsaker, Maxwell A. Sherman, Nolan Kamitaki, Alison R. Barton, Ronen E. Mukamel, Chikashi Terao, Steven A. McCarroll, Po-Ru Loh
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Cell-type-specific and disease-associated expression quantitative trait loci in the human lung Nat. Genet. (IF 30.8) Pub Date : 2024-03-28 Heini M. Natri, Christina B. Del Azodi, Lance Peter, Chase J. Taylor, Sagrika Chugh, Robert Kendle, Mei-i Chung, David K. Flaherty, Brittany K. Matlock, Carla L. Calvi, Timothy S. Blackwell, Lorraine B. Ware, Matthew Bacchetta, Rajat Walia, Ciara M. Shaver, Jonathan A. Kropski, Davis J. McCarthy, Nicholas E. Banovich
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A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast Nat. Genet. (IF 30.8) Pub Date : 2024-03-28 Austin D. Reed, Sara Pensa, Adi Steif, Jack Stenning, Daniel J. Kunz, Linsey J. Porter, Kui Hua, Peng He, Alecia-Jane Twigger, Abigail J. Q. Siu, Katarzyna Kania, Rachel Barrow-McGee, Iain Goulding, Jennifer J. Gomm, Valerie Speirs, J Louise Jones, John C. Marioni, Walid T. Khaled
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Divergent composition and transposon-silencing activity of small RNAs in mammalian oocytes Genome Biol. (IF 12.3) Pub Date : 2024-03-26 Li Hou, Wei Liu, Hongdao Zhang, Ronghong Li, Miao Liu, Huijuan Shi, Ligang Wu
Small RNAs are essential for germ cell development and fertilization. However, fundamental questions remain, such as the level of conservation in small RNA composition between species and whether small RNAs control transposable elements in mammalian oocytes. Here, we use high-throughput sequencing to profile small RNAs and poly(A)-bearing long RNAs in oocytes of 12 representative vertebrate species
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Enhancer contacts during embryonic development show diverse interaction modes and modest yet significant increases upon gene activation Nat. Genet. (IF 30.8) Pub Date : 2024-03-25 Daniel M. Ibrahim
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Eukaryotic-driven directed evolution of Cas9 nucleases Genome Biol. (IF 12.3) Pub Date : 2024-03-25 Giulia Vittoria Ruta, Matteo Ciciani, Eyemen Kheir, Michele Domenico Gentile, Simone Amistadi, Antonio Casini, Anna Cereseto
Further advancement of genome editing highly depends on the development of tools with higher compatibility with eukaryotes. A multitude of described Cas9s have great potential but require optimization for genome editing purposes. Among these, the Cas9 from Campylobacter jejuni, CjCas9, has a favorable small size, facilitating delivery in mammalian cells. Nonetheless, its full exploitation is limited
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Next-Gen GWAS: full 2D epistatic interaction maps retrieve part of missing heritability and improve phenotypic prediction Genome Biol. (IF 12.3) Pub Date : 2024-03-25 Clément Carré, Jean Baptiste Carluer, Christian Chaux, Chad Estoup-Streiff, Nicolas Roche, Eric Hosy, André Mas, Gabriel Krouk
The problem of missing heritability requires the consideration of genetic interactions among different loci, called epistasis. Current GWAS statistical models require years to assess the entire combinatorial epistatic space for a single phenotype. We propose Next-Gen GWAS (NGG) that evaluates over 60 billion single nucleotide polymorphism combinatorial first-order interactions within hours. We apply
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APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Cheng-Kuei Wu, Jia-Lin Shiu, Chao-Liang Wu, Chi-Feng Hung, Yen-Chih Ho, Yen-Tzu Chen, Sheng-Yung Tung, Cheng-Fa Yeh, Che-Hung Shen, Hungjiun Liaw, Wen-Pin Su
Replication stress converts the stalled forks into reversed forks, which is an important protection mechanism to prevent fork degradation and collapse into poisonous DNA double-strand breaks (DSBs). Paradoxically, the mechanism also acts in cancer cells to contribute to chemoresistance against various DNA-damaging agents. PARP1 binds to and is activated by stalled forks to facilitate fork reversal
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S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Alberto Bugallo, Mar Sánchez, María Fernández-García, Mónica Segurado
The S-phase checkpoint is involved in coupling DNA unwinding with nascent strand synthesis and is critical to maintain replication fork stability in conditions of replicative stress. However, its role in the specific regulation of leading and lagging strands at stalled forks is unclear. By conditionally depleting RNaseH2 and analyzing polymerase usage genome-wide, we examine the enzymology of DNA replication
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MIWI N-terminal arginines orchestrate generation of functional pachytene piRNAs and spermiogenesis Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Nicholas Vrettos, Jan Oppelt, Ansgar Zoch, Paraskevi Sgourdou, Haruka Yoshida, Brian Song, Ryan Fink, Dónal O’Carroll, Zissimos Mourelatos
N-terminal arginine (NTR) methylation is a conserved feature of PIWI proteins, which are central components of the PIWI-interacting RNA (piRNA) pathway. The significance and precise function of PIWI NTR methylation in mammals remains unknown. In mice, PIWI NTRs bind Tudor domain containing proteins (TDRDs) that have essential roles in piRNA biogenesis and the formation of the chromatoid body. Using
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The zinc-finger protein Z4 cooperates with condensin II to regulate somatic chromosome pairing and 3D chromatin organization Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Marta Puerto, Mamta Shukla, Paula Bujosa, Juan Pérez-Roldán, Mònica Torràs-Llort, Srividya Tamirisa, Albert Carbonell, Carme Solé, Joynob Akter Puspo, Christopher T Cummings, Eulàlia de Nadal, Francesc Posas, Fernando Azorín, M Jordan Rowley
Chromosome pairing constitutes an important level of genome organization, yet the mechanisms that regulate pairing in somatic cells and the impact on 3D chromatin organization are still poorly understood. Here, we address these questions in Drosophila, an organism with robust somatic pairing. In Drosophila, pairing preferentially occurs at loci consisting of numerous architectural protein binding sites
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ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Scott Bachus, Nikolas Akkerman, Lauren Fulham, Drayson Graves, Rafe Helwer, Jordan Rempel, Peter Pelka
Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as
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txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility Genome Biol. (IF 12.3) Pub Date : 2024-03-22 Hao Zhang, Ryan M. Mulqueen, Natalie Iannuzo, Dominique O. Farrera, Francesca Polverino, James J. Galligan, Julie G. Ledford, Andrew C. Adey, Darren A. Cusanovich
We develop a large-scale single-cell ATAC-seq method by combining Tn5-based pre-indexing with 10× Genomics barcoding, enabling the indexing of up to 200,000 nuclei across multiple samples in a single reaction. We profile 449,953 nuclei across diverse tissues, including the human cortex, mouse brain, human lung, mouse lung, mouse liver, and lung tissue from a club cell secretory protein knockout (CC16−/−)
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Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism Genome Biol. (IF 12.3) Pub Date : 2024-03-22 Emily M. Pujadas Liwag, Xiaolong Wei, Nicolas Acosta, Lucas M. Carter, Jiekun Yang, Luay M. Almassalha, Surbhi Jain, Ali Daneshkhah, Suhas S. P. Rao, Fidan Seker-Polat, Kyle L. MacQuarrie, Joe Ibarra, Vasundhara Agrawal, Erez Lieberman Aiden, Masato T. Kanemaki, Vadim Backman, Mazhar Adli
B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible
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Robust chromatin state annotation Genome Res. (IF 7.0) Pub Date : 2024-03-21 Mehdi Foroozandeh Shahraki, Marjan Farahbod, Maxwell W. Libbrecht
With the goal of mapping genomic activity, international projects have recently measured epigenetic activity in hundreds of cell and tissue types. Chromatin state annotations produced by segmentation and genome annotation (SAGA) methods have emerged as the predominant way to summarize these epigenomic data sets in order to annotate the genome. These chromatin state annotations are essential for many
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Global genomic diversity for All of Us Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-20 Linda Koch
A publication in Nature reports the data release of around 245,000 clinical-grade whole-genome sequences as part of the NIH’s All of Us Research Programme. Several companion papers highlight the value of better capturing global genomic diversity.
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Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis Nat. Genet. (IF 30.8) Pub Date : 2024-03-21 Sneha Mitra, Rohan Malik, Wilfred Wong, Afsana Rahman, Alexander J. Hartemink, Yuri Pritykin, Kushal K. Dey, Christina S. Leslie
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Cell subtype-specific effects of genetic variation in the Alzheimer’s disease brain Nat. Genet. (IF 30.8) Pub Date : 2024-03-21 Masashi Fujita, Zongmei Gao, Lu Zeng, Cristin McCabe, Charles C. White, Bernard Ng, Gilad Sahar Green, Orit Rozenblatt-Rosen, Devan Phillips, Liat Amir-Zilberstein, Hyo Lee, Richard V. Pearse, Atlas Khan, Badri N. Vardarajan, Krzysztof Kiryluk, Chun Jimmie Ye, Hans-Ulrich Klein, Gao Wang, Aviv Regev, Naomi Habib, Julie A. Schneider, Yanling Wang, Tracy Young-Pearse, Sara Mostafavi, David A. Bennett
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Cataloging the phylogenetic diversity of human bladder bacterial isolates Genome Biol. (IF 12.3) Pub Date : 2024-03-21 Jingjie Du, Mark Khemmani, Thomas Halverson, Adriana Ene, Roberto Limeira, Lana Tinawi, Baylie R. Hochstedler-Kramer, Melline Fontes Noronha, Catherine Putonti, Alan J. Wolfe
Although the human bladder is reported to harbor unique microbiota, our understanding of how these microbial communities interact with their human hosts is limited, mostly owing to the lack of isolates to test mechanistic hypotheses. Niche-specific bacterial collections and associated reference genome databases have been instrumental in expanding knowledge of the microbiota of other anatomical sites
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txtools: an R package facilitating analysis of RNA modifications, structures, and interactions Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Miguel Angel Garcia-Campos, Schraga Schwartz
We present txtools, an R package that enables the processing, analysis, and visualization of RNA-seq data at the nucleotide-level resolution, seamlessly integrating alignments to the genome with transcriptomic representation. txtools’ main inputs are BAM files and a transcriptome annotation, and the main output is a table, capturing mismatches, deletions, and the number of reads beginning and ending
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Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Xinglin Hu, Xingwei Huang, Yue Yang, Yuchen Sun, Yanhua Zhao, Zhijing Zhang, Dan Qiu, Yanshuang Wu, Guangming Wu, Lei Lei
The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor
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Comprehensive analysis of intramolecular G-quadruplex structures: furthering the understanding of their formalism Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Marc Farag, Liliane Mouawad
G-quadruplexes (G4) are helical structures found in guanine-rich DNA or RNA sequences. Generally, their formalism is based on a few dozen structures, which can produce some inconsistencies or incompleteness. Using the website ASC-G4, we analyzed the structures of 333 intramolecular G4s, of all types, which allowed us to clarify some key concepts and present new information. To each of the eight distinguishable
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Increased enhancer–promoter interactions during developmental enhancer activation in mammals Nat. Genet. (IF 30.8) Pub Date : 2024-03-20 Zhuoxin Chen, Valentina Snetkova, Grace Bower, Sandra Jacinto, Benjamin Clock, Atrin Dizehchi, Iros Barozzi, Brandon J. Mannion, Ana Alcaina-Caro, Javier Lopez-Rios, Diane E. Dickel, Axel Visel, Len A. Pennacchio, Evgeny Z. Kvon
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The homeobox transcription factor DUXBL controls exit from totipotency Nat. Genet. (IF 30.8) Pub Date : 2024-03-20 Maria Vega-Sendino, Felipe F. Lüttmann, Teresa Olbrich, Yanpu Chen, Carsten Kuenne, Paula Stein, Desiree Tillo, Grace I. Carey, Jiasheng Zhong, Virginia Savy, Lenka Radonova, Tianlin Lu, Bechara Saykali, Kee-Pyo Kim, Catherine N. Domingo, Leah Schüler, Stefan Günther, Mette Bentsen, Darko Bosnakovski, Hans Schöler, Michael Kyba, Tapan K. Maity, Lisa M. Jenkins, Mario Looso, Carmen J. Williams, Johnny
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Translation-dependent and independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T Cell activation Genome Res. (IF 7.0) Pub Date : 2024-03-20 Blandine C Mercier, Emmanuel Labaronne, David Cluet, Laura Guiguettaz, Nicolas Fontrodona, Alicia Bicknell, Antoine Corbin, Melanie Wencker, Fabien Aube, Laurent Modolo, Karina Jouravleva, Didier Auboeuf, Melissa J Moore, Emiliano P Ricci
mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions and through the recruitment of specific proteins to ribosomes are important determinants of mRNA turnover. However, the extent to which translation-dependent (TDD) and
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The genome of the colonial hydroid Hydractinia reveals their stem cells utilize a toolkit of evolutionarily shared genes with all animals Genome Res. (IF 7.0) Pub Date : 2024-03-20 Christine E. Schnitzler, E. Sally Chang, Justin Waletich, Gonzalo Quiroga-Artigas, Wai Yee Wong, Anh-Dao Nguyen, Sofia Barreira, Liam B. Doonan, Paul Gonzalez, Sergey Koren, James Gahan, Steven Sanders, Brian Bradshaw, Timothy DuBuc, Febrimarsa Febrimarsa, Danielle de Jong, Eric Nawrocki, Alexandra Larson, Samantha Klasfeld, Sebastian Gornik, R. Travis Moreland, Tyra Wolfsberg, Adam M Phillippy, James
Hydractinia is a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, H. symbiolongicarpus and H. echinata, placing
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Inference of selective force on house mouse genomes during secondary contact in East Asia Genome Res. (IF 7.0) Pub Date : 2024-03-20 Kazumichi Fujiwara, Shunpei Kubo, Toshinori Endo, Toyoyuki Takada, Toshihiko Shiroishi, Hitoshi Suzuki, Naoki Osada
The house mouse (Mus musculus), which is commensal to humans, has spread globally via human activities, leading to secondary contact between genetically divergent subspecies. This pattern of genetic admixture can provide insights into the selective forces at play in this well-studied model organism. Our analysis of 163 house mouse genomes, with a particular focus on East Asia, revealed substantial
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Protein domains of low sequence complexity—dark matter of the proteome Genes Dev. (IF 10.5) Pub Date : 2024-03-19 Steven L. McKnight
This perspective begins with a speculative consideration of the properties of the earliest proteins to appear during evolution. What did these primitive proteins look like, and how were they of benefit to early forms of life? I proceed to hypothesize that primitive proteins have been preserved through evolution and now serve diverse functions important to the dynamics of cell morphology and biological
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WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases Genes Dev. (IF 10.5) Pub Date : 2024-03-19 Jung-Hoon Yoon, Karthi Sellamuthu, Louise Prakash, Satya Prakash
Purified translesion synthesis (TLS) DNA polymerases (Pols) replicate through DNA lesions with a low fidelity; however, TLS operates in a predominantly error-free manner in normal human cells. To explain this incongruity, here we determine whether Y family Pols, which play an eminent role in replication through a diversity of DNA lesions, are incorporated into a multiprotein ensemble and whether the
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NFATC2IP is a mediator of SUMO-dependent genome integrity Genes Dev. (IF 10.5) Pub Date : 2024-03-19 Tiffany Cho, Lisa Hoeg, Dheva Setiaputra, Daniel Durocher
The post-translational modification of proteins by SUMO is crucial for cellular viability and mammalian development in part due to the contribution of SUMOylation to genome duplication and repair. To investigate the mechanisms underpinning the essential function of SUMO, we undertook a genome-scale CRISPR/Cas9 screen probing the response to SUMOylation inhibition. This effort identified 130 genes whose
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The evolution of modifier genes Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-19 Yoav Ram
In this Journal Club, Yoav Ram recalls how he reconciled results from his own research with the reduction principle through the help of a paper published in PNAS by Altenberg et al.
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Dynamics of ER stress-induced gene regulation in plants Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-18 Dae Kwan Ko, Federica Brandizzi
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miR-430 regulates zygotic mRNA during zebrafish embryogenesis Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Danielson Baia Amaral, Rhonda Egidy, Anoja Perera, Ariel A Bazzini
Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately. By employing SLAM-seq, a nascent mRNA labeling
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Multi-slice spatial transcriptome domain analysis with SpaDo Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Bin Duan, Shaoqi Chen, Xiaojie Cheng, Qi Liu
With the rapid advancements in spatial transcriptome sequencing, multiple tissue slices are now available, enabling the integration and interpretation of spatial cellular landscapes. Herein, we introduce SpaDo, a tool for multi-slice spatial domain analysis, including modules for multi-slice spatial domain detection, reference-based annotation, and multiple slice clustering at both single-cell and
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DANCE: a deep learning library and benchmark platform for single-cell analysis Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Jiayuan Ding, Renming Liu, Hongzhi Wen, Wenzhuo Tang, Zhaoheng Li, Julian Venegas, Runze Su, Dylan Molho, Wei Jin, Yixin Wang, Qiaolin Lu, Lingxiao Li, Wangyang Zuo, Yi Chang, Yuying Xie, Jiliang Tang
DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark
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FUS reads histone H3K36me3 to regulate alternative polyadenylation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-19 Junqi Jia, Haonan Fan, Xinyi Wan, Yuan Fang, Zhuoning Li, Yin Tang, Yanjun Zhang, Jun Huang, Dong Fang
Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3
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Experimentally evolving Drosophila erecta populations may fail to establish an effective piRNA based host defense against invading P-elements Genome Res. (IF 7.0) Pub Date : 2024-03-15 Divya Selvaraju, Filip Wierzbicki, Robert Kofler
To prevent the spread of transposable elements (TEs) hosts have developed sophisticated defense mechanisms. In mammals and invertebrates, a major defense mechanism operates through PIWI-interacting RNAs (piRNAs). To investigate the establishment of the host defence we introduced the P-element, one of the most widely studied eukaryotic transposons, into naive lines of Drosophila erecta. We monitored
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Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance Nat. Genet. (IF 30.8) Pub Date : 2024-03-15 Peng-Fei Ma, Yun-Long Liu, Cen Guo, Guihua Jin, Zhen-Hua Guo, Ling Mao, Yi-Zhou Yang, Liang-Zhong Niu, Yu-Jiao Wang, Lynn G. Clark, Elizabeth A. Kellogg, Zu-Chang Xu, Xia-Ying Ye, Jing-Xia Liu, Meng-Yuan Zhou, Yan Luo, Yang Yang, Douglas E. Soltis, Jeffrey L. Bennetzen, Pamela S. Soltis, De-Zhu Li
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MYC activates transcriptional enhancers to drive cancer progression Nat. Genet. (IF 30.8) Pub Date : 2024-03-13
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Multiplex DNA fluorescence in situ hybridization to analyze maternal vs. paternal C. elegans chromosomes Genome Biol. (IF 12.3) Pub Date : 2024-03-14 Silvia Gutnik, Jia Emil You, Ahilya N. Sawh, Aude Andriollo, Susan E. Mango
Recent advances in microscopy have enabled studying chromosome organization at the single-molecule level, yet little is known about inherited chromosome organization. Here we adapt single-molecule chromosome tracing to distinguish two C. elegans strains (N2 and HI) and find that while their organization is similar, the N2 chromosome influences the folding parameters of the HI chromosome, in particular
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Substrate specificity of Mycobacterium tuberculosis tRNA terminal nucleotidyltransferase toxin MenT3 Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-15 Jun Liu, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Mycobacterium tuberculosis transfer RNA (tRNA) terminal nucleotidyltransferase toxin, MenT3, incorporates nucleotides at the 3′-CCA end of tRNAs, blocking their aminoacylation and inhibiting protein synthesis. Here, we show that MenT3 most effectively adds CMPs to the 3′-CCA end of tRNA. The crystal structure of MenT3 in complex with CTP reveals a CTP-specific nucleotide-binding pocket. The 4-NH2 and
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Competition between sites of meiotic recombination in snakes Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-12 Kirsty Minton
A study in Science reports that corn snakes use both PRDM9 and promoter-like features to direct meiotic recombination, indicating that these are not mutually exclusive.
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Genetic contribution to heterogeneity in type 2 diabetes Nat. Genet. (IF 30.8) Pub Date : 2024-03-13 Wei Li
Genome-wide association studies of type 2 diabetes (T2D) have led to the identification of hundreds of risk loci. Through the Type 2 Diabetes Global Genomics Initiative, Suzuki et al. performed a multi-ancestry meta-analysis of T2D in 2,535,601 individuals (428,452 cases of T2D) from diverse ancestry groups: European (60.3%), East Asian (19.8%), admixed African American (10.5%), admixed Hispanic (5
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How transposable elements are spliced out Nat. Genet. (IF 30.8) Pub Date : 2024-03-13 Chiara Anania
A large part of the human genome consists of transposable elements (TEs). Most TEs do not contribute to mature transcripts, which suggests that cells might have evolved a strategy to skip TE sequences by splicing them as introns. In a study published in Nature, Ilık et al. studied 33 RNA-binding proteins involved in splicing, and found that SAFB, hnRNPC and DHX9 associated with sense LINE1 elements
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Implicating XIST in sex-biased autoimmunity Nat. Genet. (IF 30.8) Pub Date : 2024-03-13 Kyle Vogan
Autoimmune diseases exhibit a strong female sex bias in incidence, but the mechanistic basis for this differential susceptibility is poorly understood. Given previous evidence that X chromosome dosage, and specifically the long non-coding RNA XIST produced from the inactive X chromosome and its associated proteins, could be key factors underlying the increased autoimmune disease risk in females and
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Transcription factor binding site affinity and the link to phenotype Nat. Genet. (IF 30.8) Pub Date : 2024-03-13 Michael Fletcher
Genetic variation, such as single-nucleotide variants (SNVs), can alter transcription factor binding and thus phenotypes. However, the exact mechanistic bases of this process remain poorly understood. Lim et al. examine the classic model enhancer, ZRS, which regulates expression of SHH during limb development and contains SNVs that are causal for polydactyly. Using protein-binding microarray data,
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Guidance on use of race, ethnicity, and geographic origin as proxies for genetic ancestry groups in biomedical publications Nat. Genet. (IF 30.8) Pub Date : 2024-03-13 W. Gregory Feero, Robert D. Steiner, Anne Slavotinek, Tiago Faial, Michael J. Bamshad, Jehannine Austin, Bruce R. Korf, Annette Flanagin, Kirsten Bibbins-Domingo
In March 2023, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a consensus study report titled Using Population Descriptors in Genetics and Genomics Research1. Sponsored by the US National Institutes of Health, the report is more than a discussion of the use of terminology; the authors of the NASEM report suggest a tectonic shift away from current models that use race
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Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism Genome Biol. (IF 12.3) Pub Date : 2024-03-14 Chao Gu, Mao-Song Pei, Zhi-Hua Guo, Lei Wu, Kai-Jie Qi, Xue-Ping Wang, Hong Liu, Zhongchi Liu, Zhaobo Lang, Shaoling Zhang
Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here
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Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Yibo Zhu, Xingyu Mou, Yingjie Song, Qianqian Zhang, Bo Sun, Huanxiang Liu, Hong Tang, Rui Bao
The regulation of carbon metabolism and virulence is critical for the rapid adaptation of pathogenic bacteria to host conditions. In Pseudomonas aeruginosa, RccR is a transcriptional regulator of genes involved in primary carbon metabolism and is associated with bacterial resistance and virulence, although the exact mechanism is unclear. Our study demonstrates that PaRccR is a direct repressor of the
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Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Kasuen Kotagama, Acadia L Grimme, Leah Braviner, Bing Yang, Rima M Sakhawala, Guoyun Yu, Lars Kristian Benner, Leemor Joshua-Tor, Katherine McJunkin
Many microRNA (miRNA)-guided Argonaute proteins can cleave RNA (‘slicing’), even though miRNA-mediated target repression is generally cleavage-independent. Here we use Caenorhabditis elegans to examine the role of catalytic residues of miRNA Argonautes in organismal development. In contrast to previous work, mutations in presumed catalytic residues did not interfere with development when introduced
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Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Nisha Hemandhar Kumar, Verena Kluever, Emanuel Barth, Sebastian Krautwurst, Mattia Furlan, Mattia Pelizzola, Manja Marz, Eugenio F Fornasiero
A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse
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Structural basis of how MGME1 processes DNA 5′ ends to maintain mitochondrial genome integrity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Eric Y C Mao, Han-Yi Yen, Chyuan-Chuan Wu
Mitochondrial genome maintenance exonuclease 1 (MGME1) helps to ensure mitochondrial DNA (mtDNA) integrity by serving as an ancillary 5′-exonuclease for DNA polymerase γ. Curiously, MGME1 exhibits unique bidirectionality in vitro, being capable of degrading DNA from either the 5′ or 3′ end. The structural basis of this bidirectionally and, particularly, how it processes DNA from the 5′ end to assist
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CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23 Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Sabine Grüschow, Stuart McQuarrie, Katrin Ackermann, Stephen McMahon, Bela E Bode, Tracey M Gloster, Malcolm F White
CRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow
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Short tandem repeats — how microsatellites became the currency of forensic genetics Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-11 Bruce Budowle, Antti Sajantila
Short tandem repeats (STRs), also known as microsatellites, are the primary markers of forensic genetics for developing investigative leads in criminal cases and humanitarian efforts. Their variation in length and sequence provides genetic information even in samples of low quantity and quality, enabling high resolution for identification and attribution purposes, and culminating in the development
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The regulatory landscape of chromatin accessibility Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-11 Henry Ertl
A study in Nature Genetics identifies many regulators of genome-wide chromatin accessibility and then reports the mechanistic underpinnings for one of the identified transcription factors.
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Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications Nat. Rev. Genet. (IF 42.7) Pub Date : 2024-03-11 Indhu-Shree Rajan-Babu, Egor Dolzhenko, Michael A. Eberle, Jan M. Friedman