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Variation in the fitness impact of translationally optimal codons among animals Genome Res. (IF 6.2) Pub Date : 2025-02-10 Florian Bénitière, Tristan Lefébure, Laurent Duret
Early studies in invertebrate model organisms (fruit flies, nematodes) showed that their synonymous codon usage is under selective pressure to optimize translation efficiency in highly expressed genes (a process called translational selection). In contrast, mammals show little evidence of selection for translationally optimal codons. To understand this difference, we examined the use of synonymous
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Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites Genome Res. (IF 6.2) Pub Date : 2025-02-10 Patrick Wilson, Xinyang Yu, Christopher R Handelmann, Michael J Buck
The TP53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73 - the three members of the TP53 family - regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the TP53 family, we used Pioneer-seq,
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Dynamic changes in 3D chromatin structure during male gametogenesis in Arabidopsis thaliana Genome Biol. (IF 10.1) Pub Date : 2025-02-10 Zhihan Song, Qimin Xia, Minqi Yang, Tingting Yang, Yali Liu, Dingyue Wang, Jiayue Shu, Zhiyuan Liu, Yi Chi, Heming Xu, Dong Xing, Yue Zhou
Chromatin higher-order structure plays an important role in genome stability maintenance and gene transcriptional regulation; however, the dynamics of the three-dimensional (3D) chromatin in male gametophytes during the two rounds of mitosis remains elusive. Here, we use the optimized single-nucleus and low-input Hi-C methods to investigate changes in 3D chromatin structure in four types of male gametophyte
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Multi-omics analysis in primary T cells elucidates mechanisms behind disease-associated genetic loci Genome Biol. (IF 10.1) Pub Date : 2025-02-10 Chenfu Shi, Danyun Zhao, Jake Butler, Antonios Frantzeskos, Stefano Rossi, James Ding, Carlo Ferrazzano, Charlotte Wynn, Ryan Malcolm Hum, Ellie Richards, Muskan Gupta, Khadijah Patel, Chuan Fu Yap, Darren Plant, Richard Grencis, Paul Martin, Antony Adamson, Stephen Eyre, John Bowes, Anne Barton, Pauline Ho, Magnus Rattray, Gisela Orozco
Genome-wide association studies (GWAS) have uncovered the genetic basis behind many diseases and conditions. However, most of these genetic loci affect regulatory regions, making the interpretation challenging. Chromatin conformation has a fundamental role in gene regulation and is frequently used to associate potential target genes to regulatory regions. However, previous studies mostly used small
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Long-read sequencing and genome assembly of natural history collection samples and challenging specimens Genome Biol. (IF 10.1) Pub Date : 2025-02-10 Bernhard Bein, Ioannis Chrysostomakis, Larissa S. Arantes, Tom Brown, Charlotte Gerheim, Tilman Schell, Clément Schneider, Evgeny Leushkin, Zeyuan Chen, Julia Sigwart, Vanessa Gonzalez, Nur Leena W. S. Wong, Fabricio R. Santos, Mozes P. K. Blom, Frieder Mayer, Camila J. Mazzoni, Astrid Böhne, Sylke Winkler, Carola Greve, Michael Hiller
Museum collections harbor millions of samples, largely unutilized for long-read sequencing. Here, we use ethanol-preserved samples containing kilobase-sized DNA to show that amplification-free protocols can yield contiguous genome assemblies. Additionally, using a modified amplification-based protocol, employing an alternative polymerase to overcome PCR bias, we assemble the 3.1 Gb maned sloth genome
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The African Animal Breeding Network as a pathway towards genetic improvement of livestock Nat. Genet. (IF 31.7) Pub Date : 2025-02-10 Appolinaire Djikeng, Victor E. Olori, Isidore Houaga, Samuel E. Aggrey, Okeyo Mwai, Eveline M. Ibeagha-Awemu, Raphael Mrode, Mizeck G. G. Chagunda, Christian K. Tiambo, Romdhane Rekaya, Oyenkanmi Nash, Zabron Nziku, Oluyinka Opoola, Mapholi Ntanganedzeni, Chinyere Ekine-Dzivenu, Alexander Kahi, Tobias Okeno, John M. Hickey, Negussie Enyew, Edward J. O. Rege
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Oncofetal reprogramming drives phenotypic plasticity in WNT-dependent colorectal cancer Nat. Genet. (IF 31.7) Pub Date : 2025-02-10 Slim Mzoughi, Megan Schwarz, Xuedi Wang, Deniz Demircioglu, Gulay Ulukaya, Kevin Mohammed, Habiba Zorgati, Denis Torre, Lewis E. Tomalin, Federico Di Tullio, Carlos Company, Yuliia Dramaretska, Marc Leushacke, Bruno Giotti, Tamsin RM Lannagan, Daniel Lozano-Ojalvo, Panagiotis Karras, Peter B. Vermeulen, Dan Hasson, Robert Sebra, Alexander M. Tsankov, Owen J. Sansom, Jean-Christophe Marine, Nick Barker
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Prioritizing effector genes at trait-associated loci using multimodal evidence Nat. Genet. (IF 31.7) Pub Date : 2025-02-10 Marijn Schipper, Christiaan A. de Leeuw, Bernardo A. P. C. Maciel, Douglas P. Wightman, Nikki Hubers, Dorret I. Boomsma, Michael C. O’Donovan, Danielle Posthuma
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Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups Nat. Genet. (IF 31.7) Pub Date : 2025-02-10 Thomas J. Hoffmann, Rebecca E. Graff, Ravi K. Madduri, Alex A. Rodriguez, Clinton L. Cario, Karen Feng, Yu Jiang, Anqi Wang, Robert J. Klein, Brandon L. Pierce, Scott Eggener, Lin Tong, William Blot, Jirong Long, Louisa B. Goss, Burcu F. Darst, Timothy Rebbeck, Joseph Lachance, Caroline Andrews, Akindele O. Adebiyi, Ben Adusei, Oseremen I. Aisuodionoe-Shadrach, Pedro W. Fernandez, Mohamed Jalloh, Rohini
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Oncofetal reprogramming induces phenotypic heterogeneity in colorectal cancer Nat. Genet. (IF 31.7) Pub Date : 2025-02-07
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Publisher Correction: Functional innovation through new genes as a general evolutionary process Nat. Genet. (IF 31.7) Pub Date : 2025-02-07 Shengqian Xia, Jianhai Chen, Deanna Arsala, J. J. Emerson, Manyuan Long
Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-02059-0, published online 28 January 2025.
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Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR–ncPRC1.1 Genes Dev. (IF 7.5) Pub Date : 2025-02-07 Joyce Wolf van der Meer, Axelle Larue, Jan A. van der Knaap, Gillian E. Chalkley, Ayestha Sijm, Leila Beikmohammadi, Elena N. Kozhevnikova, Aniek van der Vaart, Ben C. Tilly, Karel Bezstarosti, Dick H.W. Dekkers, Wouter A.S. Doff, P. Jantine van de Wetering-Tieleman, Kristina Lanko, Tahsin Stefan Barakat, Tim Allertz, Jeffrey van Haren, Jeroen A.A. Demmers, Yaser Atlasi, C. Peter Verrijzer
Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, it remains unclear which of USP7's pleiotropic functions are relevant for neurodevelopment. Here, we present a combination of quantitative proteomics, transcriptomics, and epigenomics to define the USP7 regulatory circuitry during neuronal differentiation.
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A systematic survey of TF function in E. coli suggests RNAP stabilization is a prevalent strategy for both repressors and activators. Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-08 Sunil Guharajan,Vinuselvi Parisutham,Robert C Brewster
Transcription factors (TFs) are often classified as activators or repressors, yet these context-dependent labels are inadequate to predict quantitative profiles that emerge across different promoters. A mechanistic understanding of how different regulatory sequences shape TF function is challenging due to the lack of systematic genetic control in endogenous genes. To address this, we use a library
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NEAT1-mediated regulation of proteostasis and mRNA localization impacts autophagy dysregulation in Rett syndrome. Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-08 Edilene Siqueira,Cecilia D Velasco,Ariadna Tarrasón,Marta Soler,Tara Srinivas,Fernando Setién,Cristina Oliveira-Mateos,Marta Casado-Pelaez,Laura Martinez-Verbo,Judith Armstrong,Manel Esteller,Letícia F Alves,Artur Llobet,Sonia Guil
Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by loss-of-function mutations in the MECP2 gene, resulting in diverse cellular dysfunctions. Here, we investigated the role of the long noncoding RNA (lncRNA) NEAT1 in the context of MeCP2 deficiency using human neural cells and RTT patient samples. Through single-cell RNA sequencing and molecular analyses, we found that NEAT1
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Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers. Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-08 Tomas Goncalves,Siobhan Cunniffe,Tiffany S Ma,Natalie Mattis,Andrew W Rose,Thomas Kent,David R Mole,Helene E B Geiller,Linda van Bijsterveldt,Timothy C Humphrey,Ester M Hammond,Richard J Gibbons,David Clynes,Anna M Rose
The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent mechanism for immortalization in cancer cells and is commonly activated in low-grade and high-grade glioma, as well as osteosarcoma. The ALT pathway can be activated under various conditions and has often been shown to include mutational loss of ATRX. However, this is insufficient in isolation and so other cellular event
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The ribosome as a platform to coordinate mRNA decay. Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-08 Martin B D Müller,Thomas Becker,Timo Denk,Satoshi Hashimoto,Toshifumi Inada,Roland Beckmann
Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay processes. Recent advances have revealed that the ribosome plays a central role in coordinating mRNA decay, challenging the traditional view that free mRNA is the primary substrate for degradation. This review examines the mechanisms whereby ribosomes facilitate
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CRISPuRe-seq: pooled screening of barcoded ribonucleoprotein reporters reveals regulation of RNA polymerase III transcription by the integrated stress response via mTOR. Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-08 David T Harris,Calvin H Jan
Genetic screens using CRISPR (Clustered Regularly Interspaced Palindromic Repeats) provide valuable information about gene function. Nearly all pooled screening technologies rely on the cell to link genotype to phenotype, making it challenging to assay mechanistically informative, biochemically defined phenotypes. Here, we present CRISPuRe-seq (CRISPR PuRification), a novel pooled screening strategy
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Unveiling heterogeneity in rare cells by combining RNA-based sorting and scRNA-seq Nat. Genet. (IF 31.7) Pub Date : 2025-02-07 Madison Wahlsten, Sydney M. Shaffer
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SpatialLeiden: spatially aware Leiden clustering Genome Biol. (IF 10.1) Pub Date : 2025-02-07 Niklas Müller-Bötticher, Shashwat Sahay, Roland Eils, Naveed Ishaque
Clustering can identify the natural structure that is inherent to measured data. For single-cell omics, clustering finds cells with similar molecular phenotype after which cell types are annotated. Leiden clustering is one of the algorithms of choice in the single-cell community. In the field of spatial omics, Leiden is often categorized as a “non-spatial” clustering method. However, we show that by
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Spatial miRNomics: towards the integration of microRNAs in spatial biology Nat. Rev. Genet. (IF 39.1) Pub Date : 2025-02-06 Agustín Robles-Remacho, Mats Nilsson
Spatial transcriptomics tools enable the detection and localization of hundreds to thousands of transcripts in biological tissues. However, most technologies are not designed to detect microRNAs. Existing technologies should be expanded to incorporate these key molecular regulators and enable more-comprehensive transcriptomic studies that will shape the new field of spatial miRNomics. In this Comment
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CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids Genome Biol. (IF 10.1) Pub Date : 2025-02-06 Eleonora Cappelletti, Francesca M. Piras, Marialaura Biundo, Elena Raimondi, Solomon G. Nergadze, Elena Giulotto
While CENP-A is the epigenetic determinant of the centromeric function, the role of CENP-B, a centromeric protein binding a specific DNA sequence, the CENP-B-box, remains elusive. In the few mammalian species analyzed so far, the CENP-B box is contained in the major satellite repeat that is present at all centromeres, with the exception of the Y chromosome. We previously demonstrated that, in the genus
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Kernel-bounded clustering for spatial transcriptomics enables scalable discovery of complex spatial domains Genome Res. (IF 6.2) Pub Date : 2025-02-05 Hang Zhang, Yi Zhang, Kai Ming Ting, Jie Zhang, Qiuran Zhao
Spatial transcriptomics are a collection of technologies that have enabled characterization of gene expression profiles and spatial information in tissue samples. Existing methods for clustering spatial transcriptomics data have primarily focused on data transformation techniques to represent the data suitably for subsequent clustering analysis, often using an existing clustering algorithm. These methods
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SETD2 loss-of-function uniquely sensitizes cells to epigenetic targeting of NSD1-directed H3K36 methylation Genome Biol. (IF 10.1) Pub Date : 2025-02-05 Ryan T. Wagner, Ryan A. Hlady, Xiaoyu Pan, Liguo Wang, Sungho Kim, Xia Zhao, Louis Y. El Khoury, Shafiq Shaikh, Jian Zhong, Jeong-Heon Lee, Jolanta Grembecka, Tomasz Cierpicki, Thai H. Ho, Keith D. Robertson
SETD2 is the sole epigenetic factor responsible for catalyzing histone 3, lysine 36, tri-methylation (H3K36me3) in mammals. Its role in regulating cellular processes such as RNA splicing, DNA repair, and spurious transcription initiation underlies its broader tumor suppressor function. SETD2 mutation promotes the epithelial-mesenchymal transition and is clinically associated with adverse outcomes highlighting
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The double life of mammalian DNA replication origins Genes Dev. (IF 7.5) Pub Date : 2025-02-04 Olivier Hyrien, Guillaume Guilbaud, Torsten Krude
Mammalian DNA replication origins have been historically difficult to identify and their determinants are still unresolved. Here, we first review methods developed over the last decades to map replication initiation sites either directly via initiation intermediates or indirectly via determining replication fork directionality profiles. We also discuss the factors that may specify these sites as replication
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A feedback amplifier circuit with Notch and E2A orchestrates T-cell fate and suppresses the innate lymphoid cell lineages during thymic ontogeny Genes Dev. (IF 7.5) Pub Date : 2025-02-04 Kazuko Miyazaki, Kenta Horie, Hitomi Watanabe, Reiko Hidaka, Rinako Hayashi, Norihito Hayatsu, Kentaro Fujiwara, Rei Kuwata, Takuya Uehata, Yotaro Ochi, Makoto Takenaka, Risa Karakida Kawaguchi, Koichi Ikuta, Osamu Takeuchi, Seishi Ogawa, Katsuto Hozumi, Georg A. Holländer, Gen Kondoh, Taishin Akiyama, Masaki Miyazaki
External signals from the thymic microenvironment and the activities of lineage-specific transcription factors (TFs) instruct T-cell versus innate lymphoid cell (ILC) fates. However, mechanistic insights into how factors such as Notch1–Delta-like-4 (Dll4) signaling and E-protein TFs collaborate to establish T-cell identity remain rudimentary. Using multiple in vivo approaches and single-cell multiome
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Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Brianna Bibel, Tushar Raskar, Mary Couvillion, Muhoon Lee, Jordan I Kleinman, Nono Takeuchi-Tomita, L Stirling Churchman, James S Fraser, Danica Galonić Fujimori
The antibiotics chloramphenicol (CHL) and oxazolidinones, including linezolid (LZD), are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored
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Two temperature-responsive RNAs act in concert: the small RNA CyaR and the mRNA ompX Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 David A Guanzon, Stephan Pienkoß, Vivian B Brandenburg, Jennifer Röder, Daniel Scheller, Alisa Dietze, Andrea Wimbert, Christian Twittenhoff, Franz Narberhaus
Bacterial pathogens, such as Yersinia pseudotuberculosis, encounter temperature fluctuations during host infection and upon return to the environment. These temperature shifts impact RNA structures globally. While previous transcriptome-wide studies have focused on RNA thermometers in the 5′-untranslated region of virulence-related messenger RNAs, our investigation revealed temperature-driven structural
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Site-specific free energy surface parameters from single-molecule fluorescence measurements of exciton-coupled (iCy3)2 dimer probes positioned at DNA replication fork junctions Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Jack Maurer, Claire S Albrecht, Peter H von Hippel, Andrew H Marcus
Single-stranded–double-stranded DNA (ss–dsDNA) replication forks and primer-template junctions are important recognition sites for the assembly and function of proteins involved in DNA replication, recombination, and repair. DNA ‘breathing’ – i.e. thermally induced local fluctuations of the sugar-phosphate backbones and bases – can populate metastable conformational macrostates at positions near such
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Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance and male germ cell survival Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Yasuhisa Munakata, Mengwen Hu, Yuka Kitamura, Raissa G Dani, Adam L Bynder, Amelia S Fritz, Richard M Schultz, Satoshi H Namekawa
The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGOs) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase
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Large serine integrases utilise scavenged phage proteins as directionality cofactors Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Abdulrazak Alsaleh, Alexandria Holland, Heewhan Shin, Tania Pena Reyes, Aron Baksh, Oluwateniola T Taiwo-Aiyerin, Ying Pigli, Phoebe A Rice, Femi J Olorunniji
Recombination directionality factors (RDFs) for large serine integrases (LSIs) are cofactor proteins that control the directionality of recombination to favour excision over insertion. Although RDFs are predicted to bind their cognate LSIs in similar ways, there is no overall common structural theme across LSI RDFs, leading to the suggestion that some of them may be moonlighting proteins with other
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A gate-clamp mechanism for ssDNA translocation by DdmD in Vibrio cholerae plasmid defense Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Ruoyu Li, Yusong Liu, Haishan Gao, Zhonghui Lin
The DdmDE antiplasmid system, consisting of the helicase-nuclease DdmD and the prokaryotic Argonaute (pAgo) protein DdmE, plays a crucial role in defending Vibrio cholerae against plasmids. Guided by DNA, DdmE specifically targets plasmids, disassembles the DdmD dimer, and forms a DdmD–DdmE handover complex to facilitate plasmid degradation. However, the precise ATP-dependent DNA translocation mechanism
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zol and fai: large-scale targeted detection and evolutionary investigation of gene clusters Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-05 Rauf Salamzade, Patricia Q Tran, Cody Martin, Abigail L Manson, Michael S Gilmore, Ashlee M Earl, Karthik Anantharaman, Lindsay R Kalan
Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai and zol, which together enable large-scale comparative analysis of different types of gene clusters and mobile-genetic elements, such as biosynthetic gene clusters (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference
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Integrating ELSI study teams in paediatric genomic research efforts Nat. Rev. Genet. (IF 39.1) Pub Date : 2025-02-03 Raquel G. Hernandez, Simoné Guambaña, Melissa W. VonDran, Patrick M. Van Hoose, Thomas J. Bell, Melissa A. Faith
Addressing ethical, legal and social implications (ELSI) in genomics requires early integration of specialized teams to enhance community engagement, address disparities and promote health equity. Lessons learnt from the human Developmental Genotype-Tissue Expression (dGTEx) project show how implementing a collaborative framework can support genomic discovery. The promise of paediatric genomics depends
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MAAT: a new nonparametric Bayesian framework for incorporating multiple functional annotations in transcriptome-wide association studies Genome Biol. (IF 10.1) Pub Date : 2025-02-04 Han Wang, Xiang Li, Teng Li, Zhe Li, Pak Chung Sham, Yan Dora Zhang
Transcriptome-wide association study (TWAS) has emerged as a powerful tool for translating the myriad variations identified by genome-wide association studies (GWAS) into regulated genes in the post-GWAS era. While integrating annotation information has been shown to enhance power, current annotation-assisted TWAS tools predominantly focus on epigenomic annotations. When including more annotations
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Quantifying cell divisions along evolutionary lineages in cancer Nat. Genet. (IF 31.7) Pub Date : 2025-02-04 Martin Blohmer, David M. Cheek, Wei-Ting Hung, Maria Kessler, Foivos Chatzidimitriou, Jiahe Wang, William Hung, I-Hsiu Lee, Alexander N. Gorelick, Emma CE Wassenaar, Ching-Yeuh Yang, Yi-Chen Yeh, Hsiang-Ling Ho, Dorothee Speiser, Maria M. Karsten, Michael Lanuti, Sara I. Pai, Onno Kranenburg, Jochen K. Lennerz, Teh-Ying Chou, Matthias Kloor, Kamila Naxerova
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Corrigendum: Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Núria de la Iglesia, Genevieve Konopka, Sidharth V. Puram, Jennifer A. Chan, Robert M. Bachoo, Mingjian J. You, David E. Levy, Ronald A. DePinho, Azad Bonni
Genes & Development 22: 449–462 (2008)
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LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos
The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes. Distal junctions (DJs) are
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E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant
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NKX2.2 and KLF4 cooperate to regulate α-cell identity Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel
Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet
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Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson
The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female
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Alternative splicing controls pan-neuronal homeobox gene expression Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert
The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 (“CASP of nematodes”)
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Metabolic regulation in adult and aging skeletal muscle stem cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Vittorio Sartorelli, Veronica Ciuffoli
Adult stem cells maintain homeostasis and enable regeneration of most tissues. Quiescence, proliferation, and differentiation of stem cells and their progenitors are tightly regulated processes governed by dynamic transcriptional, epigenetic, and metabolic programs. Previously thought to merely reflect a cell's energy state, metabolism is now recognized for its critical regulatory functions, controlling
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LINE-1, the NORth star of nucleolar organization Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Misaki Matsuo, Gael Cristofari
Long interspersed element-1 (LINE-1) retrotransposons are abundant transposable elements in mammals and significantly influence chromosome structure, chromatin organization, and 3D genome architecture. In this issue of Genes & Development, Ataei et al. (doi:10.1101/gad.351979.124) identify a homininae-specific LINE-1 element within nucleolar organizer regions (NORs) that is specifically transcribed
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Introducing the Global Alliance for Spatial Technologies (GESTALT) Nat. Genet. (IF 31.7) Pub Date : 2025-02-03 Jasmine T. Plummer, Ioannis S. Vlachos, Luciano G. Martelotto
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Fine-scale population structure and widespread conservation of genetic effect sizes between human groups across traits Nat. Genet. (IF 31.7) Pub Date : 2025-02-03 Sile Hu, Lino A. F. Ferreira, Sinan Shi, Garrett Hellenthal, Jonathan Marchini, Daniel J. Lawson, Simon R. Myers
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A barley pan-transcriptome reveals layers of genotype-dependent transcriptional complexity Nat. Genet. (IF 31.7) Pub Date : 2025-02-03 Wenbin Guo, Miriam Schreiber, Vanda B. Marosi, Paolo Bagnaresi, Morten Egevang Jørgensen, Katarzyna B. Braune, Ken Chalmers, Brett Chapman, Viet Dang, Christoph Dockter, Anne Fiebig, Geoffrey B. Fincher, Agostino Fricano, John Fuller, Allison Haaning, Georg Haberer, Axel Himmelbach, Murukarthick Jayakodi, Yong Jia, Nadia Kamal, Peter Langridge, Chengdao Li, Qiongxian Lu, Thomas Lux, Martin Mascher
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Genomics of rare diseases in the Greater Middle East Nat. Genet. (IF 31.7) Pub Date : 2025-02-03 Ikram Chekroun, Shruti Shenbagam, Mohamed A. Almarri, Younes Mokrab, Mohammed Uddin, Omer S. Alkhnbashi, Maha S. Zaki, Hossein Najmabadi, Kimia Kahrizi, Khalid A. Fakhro, Naif A. M. Almontashiri, Fahad R. Ali, Uğur Özbek, Bruno Reversade, Fowzan S. Alkuraya, Alawi Alsheikh-Ali, Ahmad N. Abou Tayoun
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Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis Nat. Genet. (IF 31.7) Pub Date : 2025-02-03 Annika Vannan, Ruqian Lyu, Arianna L. Williams, Nicholas M. Negretti, Evan D. Mee, Joseph Hirsh, Samuel Hirsh, Niran Hadad, David S. Nichols, Carla L. Calvi, Chase J. Taylor, Vasiliy. V. Polosukhin, Ana P. M. Serezani, A. Scott McCall, Jason J. Gokey, Heejung Shim, Lorraine B. Ware, Matthew J. Bacchetta, Ciara M. Shaver, Timothy S. Blackwell, Rajat Walia, Jennifer M. S. Sucre, Jonathan A. Kropski,
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A novel decomposer-exploiter interaction framework of plant residue microbial decomposition Genome Biol. (IF 10.1) Pub Date : 2025-02-03 Youzhi Miao, Wei Wang, Huanhuan Xu, Yanwei Xia, Qingxin Gong, Zhihui Xu, Nan Zhang, Weibing Xun, Qirong Shen, Ruifu Zhang
Plant residue microbial decomposition, subject to significant environmental regulation, represents a crucial ecological process shaping and cycling the largest terrestrial soil organic carbon pool. However, the fundamental understanding of the functional dynamics and interactions between the principal participants, fungi and bacteria, in natural habitats remains limited. In this study, the evolution
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Multi-INTACT: integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits Genome Biol. (IF 10.1) Pub Date : 2025-02-03 Jeffrey Okamoto, Xianyong Yin, Brady Ryan, Joshua Chiou, Francesca Luca, Roger Pique-Regi, Hae Kyung Im, Jean Morrison, Charles Burant, Eric B. Fauman, Markku Laakso, Michael Boehnke, Xiaoquan Wen
We present multi-integration of transcriptome-wide association studies and colocalization (Multi-INTACT), an algorithm that models multiple “gene products” (e.g., encoded RNA transcript and protein levels) to implicate causal genes and relevant gene products. In simulations, Multi-INTACT achieves higher power than existing methods, maintains calibrated false discovery rates, and detects the true causal
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Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells Genome Biol. (IF 10.1) Pub Date : 2025-02-03 Dingbo Zhang, Fiona Parth, Laura Matos da Silva, Teng-Cheong Ha, Axel Schambach, Jens Boch
Base editors are precise editing tools that employ deaminases to modify target DNA bases. The DYW-family of cytosine deaminases is structurally and phylogenetically distinct and might be harnessed for genome editing tools. We report a novel CRISPR/Cas9-cytosine base editor using SsdA, a DYW-like deaminase and bacterial toxin. A G103S mutation in SsdA enhances C-to-T editing efficiency while reducing
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A fully phased octoploid strawberry genome reveals the evolutionary dynamism of centromeric satellites Genome Biol. (IF 10.1) Pub Date : 2025-02-03 Xin Jin, Haiyuan Du, Maoxian Chen, Xu Zheng, Yiying He, Andan Zhu
We systematically examine the application of different phasing strategies to decrypt strawberry genome organization and produce a fully phased and accurate reference genome for Fragaria x ananassa cv. “EA78” (2n = 8x = 56). We identify 147 bp canonical centromeric repeats across 50 strawberry chromosomes and uncover the formation of six neocentromeres through centromere turnover. Our findings indicate
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The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases Genome Res. (IF 6.2) Pub Date : 2025-02-03 Giulia F. Del Gobbo, Kym M. Boycott
Long-read sequencing (LRS) is a promising technology positioned to study the significant proportion of rare diseases (RDs) that remain undiagnosed as it addresses many of the limitations of short-read sequencing, detecting and clarifying additional disease-associated variants that may be missed by the current standard diagnostic workflow for RDs. Some key areas where additional diagnostic yields may
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Antagonistic roles by the conserved nuclear poly(A)-binding proteins PABPN1 and ZC3H14 in nuclear RNA surveillance Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Mélodie Latour, Lauren Kwiatek, Anne-Marie Landry-Voyer, François Bachand
Most eukaryotic genomes are transcribed pervasively, thereby producing an array of long non-coding RNAs (lncRNAs) in addition to protein-coding mRNAs. A large fraction of these lncRNAs is targeted by polyadenylation-dependent decay via the poly(A)-binding protein nuclear 1 (PABPN1) and the RNA exosome. Yet, how PABPN1 contributes to nuclear RNA surveillance by facilitating lncRNA turnover by the RNA
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The membrane-targeting-sequence motif is required for exhibition of recessive resurrection in Escherichia coli RNase E Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Papri Basak, Manjula Ekka, Apuratha Pandiyan, Smriti Tandon, Jayaraman Gowrishankar
The essential homotetrameric endoribonuclease RNase E of Escherichia coli participates in global RNA turnover as well as stable RNA maturation. The protomer’s N-terminal half (residues 1–529) bears the catalytic, allosteric, and tetramerization domains, including the active site residues D303 and D346. The C-terminal half (CTH, residues 530–1061) is dispensable for viability. We have previously described
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Local structural dynamics of Rad51 protomers revealed by cryo-electron microscopy of Rad51-ssDNA filaments Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Jie Liu, Steven K Gore, Wolf-Dietrich Heyer
Homologous recombination (HR) is a high-fidelity repair mechanism for double-strand breaks. Rad51 is the key enzyme that forms filaments on single-stranded DNA (ssDNA) to catalyze homology search and DNA strand exchange in recombinational DNA repair. In this study, we employed single-particle cryogenic electron microscopy (cryo-EM) to ascertain the density map of the wild-type budding yeast Rad51-ssDNA
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The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Amitabh Ranjan, Sandy Mattijssen, Nithin Charlly, Isabel Cruz Gallardo, Leah F Pitman, Jennifer C Coleman, Maria R Conte, Richard J Maraia
LARP4 interacts with poly(A)-binding protein (PABP) to protect messenger RNAs (mRNAs) from deadenylation and decay, and recent data indicate it can direct the translation of functionally related mRNA subsets. LARP4 was known to bind RACK1, a ribosome-associated protein, although the specific regions involved and relevance had been undetermined. Here, through a combination of in-cell and in vitro methodologies
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mRNA-LM: full-length integrated SLM for mRNA analysis Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Sizhen Li, Shahriar Noroozizadeh, Saeed Moayedpour, Lorenzo Kogler-Anele, Zexin Xue, Dinghai Zheng, Fernando Ulloa Montoya, Vikram Agarwal, Ziv Bar-Joseph, Sven Jager
The success of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) messenger RNA (mRNA) vaccine has led to increased interest in the design and use of mRNA for vaccines and therapeutics. Still, selecting the most appropriate mRNA sequence for a protein remains a challenge. Several recent studies have shown that the specific mRNA sequence can have a significant impact on the translation efficiency
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Structural and mechanistic insights into the activation of a short prokaryotic argonaute system from archaeon Sulfolobus islandicus Nucleic Acids Res. (IF 16.6) Pub Date : 2025-02-03 Zhikang Dai, Yu Chen, Zeyuan Guan, Xueting Chen, Keyi Tan, Kaiyue Yang, Xuhui Yan, Yidong Liu, Zhou Gong, Wenyuan Han, Tingting Zou
Prokaryotic Argonaute proteins (pAgos) defend the host against invading nucleic acids, including plasmids and viruses. Short pAgo systems confer immunity by inducing cell death upon detecting invading nucleic acids. However, the activation mechanism of the SiAgo system, comprising a short pAgo from the archaeon Sulfolobus islandicus and its associated proteins SiAga1 and SiAga2, remains largely unknown
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Author Correction: The NAT1–bHLH110–CER1/CER1L module regulates heat stress tolerance in rice Nat. Genet. (IF 31.7) Pub Date : 2025-01-31 Hai-Ping Lu, Xue-Huan Liu, Mei-Jing Wang, Qiao-Yun Zhu, Yu-Shu Lyu, Jian-Hang Xu, Jian-Xiang Liu
Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-02065-2, published online 14 January 2025.