Genome Biology最新文献

{"title":"Antisense transcription can induce expression memory via stable promoter repression.","authors":"Verena Mutzel, Till Schwämmle, Svearike Oeverdieck, Lucija Librenjak, Benedikt Boesen, Melissa Bothe, Rutger A F Gjaltema, Ilona Dunkel, Gemma Noviello, Edda G Schulz","doi":"10.1186/s13059-025-03875-1","DOIUrl":"10.1186/s13059-025-03875-1","url":null,"abstract":"<p><strong>Background: </strong>The capacity of cells to retain a memory of previous signals enables acquisition of unique fates and adaptation to their environment. The underlying gene expression memory can arise from mutual repression of two genes, forming a toggle switch. Mutual repression can occur at antisense loci, where convergent genes repress each other in cis. The conditions for generating expression memory via antisense transcription remain poorly understood. To address this question, we combine mathematical modeling, genomics and a synthetic biology approach.</p><p><strong>Results: </strong>Simulations demonstrate stable memory emergence when both genes in an antisense pair transcribe via the convergent promoter and induce a stable repressive chromatin state. Genome-wide analysis of nascent transcription supports antisense-mediated promoter repression, since promoter-overlapping antisense gene pairs exhibit mutually exclusive expression. Through constructing a synthetic antisense locus in mESCs, we demonstrate that antisense transcription can induce stable repression, a key prerequisite for memory. Repression stability increases during mESC differentiation, highlighting cell type-specific epigenetic memory.</p><p><strong>Conclusions: </strong>Our work establishes a quantitative framework which predicts that antisense-mediated cis-memory can arise within physiologically relevant conditions, and shows that a biological phenomenon with kinetics in the range of weeks can emerge from the interplay of multiple faster molecular processes. This framework, combined with our experimental findings, demonstrates how antisense transcription can encode stable gene expression states. Our discovery that stem cells adjust their memory capacity during differentiation may clarify mechanisms underlying stemness maintenance.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":"430"},"PeriodicalIF":12.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ST-FFPE-mIF: integrating spatial transcriptomics and multiplex immunofluorescence in formalin-fixed paraffin-embedded tissues using Stereo-seq.","authors":"Xue Zhang, Meng Zhang, Yuan Xu, Yangyang Song, Xingfeng Yang, Yanan Wu, Xuelin Zhao, Dongsheng Ran, Xin Liu, Huaqiang Huang, Wenxiao Lei, Hongyan Li, Yongfen Zhang, Feng Xi, Guibo Li, Xing Liu, Luohao Xu, Ao Chen, Sha Liao, Jiajun Zhang","doi":"10.1186/s13059-025-03900-3","DOIUrl":"10.1186/s13059-025-03900-3","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"428"},"PeriodicalIF":12.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomic alignment, integration, and 3D reconstruction by STAIR.","authors":"Yuanyuan Yu, Zhi Xie","doi":"10.1186/s13059-025-03895-x","DOIUrl":"10.1186/s13059-025-03895-x","url":null,"abstract":"<p><p>Merging multiple slices into a unified 3D atlas is a significant challenge in spatial transcriptomics. Here, we introduce STAIR, an end-to-end solution for alignment, integration, and 3D reconstruction. STAIR employs a heterogeneous graph attention network with spot-level and slice-level attention mechanisms to achieve a unified embedding space and guide unsupervised 3D reconstruction. We demonstrate STAIR's marked improvements in feature integration and 2D alignment across samples and platforms compared to previous methods. Furthermore, STAIR shows first-of-its-kind performance in z-axis reconstruction of parallel slices and seamlessly integrates new slices into existing 3D atlases, providing novel biological insights from a 3D perspective.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"427"},"PeriodicalIF":12.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct roles of histone H2B ubiquitination at promoters and coding regions of Pol II-transcribed stress genes.","authors":"Rubén Barrios, Montserrat Vega, Rebeca Gracia-Domingo, Susanna Boronat, Sarela García-Santamarina, Jason C Tanny, José Ayté, Elena Hidalgo","doi":"10.1186/s13059-025-03891-1","DOIUrl":"10.1186/s13059-025-03891-1","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"419"},"PeriodicalIF":12.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AP1 is a pioneer transcription factor that programmes cell fate through MADS-domain protein tetramerisation.","authors":"Xiaocai Xu, Manuel Neumann, Frederic Carew, Peilin Chen, Caroline Braeuning, Chloe Zubieta, Jose M Muino, Cezary Smaczniak, Kerstin Kaufmann","doi":"10.1186/s13059-025-03884-0","DOIUrl":"10.1186/s13059-025-03884-0","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"418"},"PeriodicalIF":12.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylome-wide association studies and epigenetic biomarker development for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland participants.","authors":"Josephine A Robertson, Jakub Bajzik, Spyros Vernardis, Aleksandra D Chybowska, Daniel L McCartney, Arturas Grauslys, Jure Mur, Hannah M Smith, Archie Campbell, Camilla Drake, Hannah Grant, Jamie Pearce, Tom C Russ, Poppy Adkin, Matthew White, Charles Brigden, Christoph B Messner, David J Porteous, Caroline Hayward, Simon R Cox, Aleksej Zelezniak, Markus Ralser, Matthew R Robinson, Riccardo E Marioni","doi":"10.1186/s13059-025-03892-0","DOIUrl":"10.1186/s13059-025-03892-0","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"417"},"PeriodicalIF":12.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.","authors":"Khanh B Trang, Prabhat Sharma, Laura Cook, Zachary Mount, Rajan M Thomas, Nikhil N Kulkarni, Emylette Cruz Cabrera, Suzanna Rachimi, Matthew C Pahl, James A Pippin, Chun Su, Klaus H Kaestner, Joan M O'Brien, Yadav Wagley, Kurt D Hankenson, Ashley Jermusyk, Jason W Hoskins, Laufey T Amundadottir, Mai Xu, Kevin M Brown, Stewart A Anderson, Wenli Yang, Paul M Titchenell, Patrick Seale, Babette S Zemel, Alessandra Chesi, Neil Romberg, Megan K Levings, Struan F A Grant, Andrew D Wells","doi":"10.1186/s13059-025-03880-4","DOIUrl":"10.1186/s13059-025-03880-4","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"414"},"PeriodicalIF":12.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying cell-type-specific spatially variable genes with ctSVG.","authors":"Haotian Zhuang, Xinyi Shang, Wenpin Hou, Zhicheng Ji","doi":"10.1186/s13059-025-03870-6","DOIUrl":"10.1186/s13059-025-03870-6","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"416"},"PeriodicalIF":12.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling genome- and immunome-wide genetic diversity in modern and historical Jaguars.","authors":"René Meißner, Sven Winter, Jean Pierre Elbers, Martin Plášil, Ján Futas, Elmira Mohandesan, Muhammad Bilal Sharif, Petr Horin, Stefan Prost, Pamela Burger","doi":"10.1186/s13059-025-03868-0","DOIUrl":"10.1186/s13059-025-03868-0","url":null,"abstract":"<p><strong>Background: </strong>The jaguar (Panthera onca) is a keystone species within diverse ecosystems ranging from dense rainforests to open grasslands across Central and South America. However, its populations are declining rapidly due to anthropogenic actions, such as deforestation and poaching. Here we investigate the effects of this decline on genetic diversity and genetic health. Utilizing both modern and historical museum samples, we infer population structure and immunome variability in 25 jaguars to identify unique genetic diversity that can inform targeted conservation efforts.</p><p><strong>Results: </strong>Our genome-wide analyses identifies three distinct geographic populations: Central America, South American lowlands, and South American highlands. Modern samples that exhibit lower levels of heterozygosity also show higher levels of inbreeding. The South American lowland population shows the lowest levels of inbreeding, while the highland population exhibits the lowest overall immunome-wide variability. However, the innate (Natural Killer Cell Complex, Toll-Like Receptor) and adaptive (Major Histocompatibility Complex Class II) immune genes, which are crucial for adaptive responses and disease resilience, show high diversity in terms of heterozygosity and haplotype diversity in individuals of all three populations.</p><p><strong>Conclusions: </strong>South American highland and Central American jaguars face significant threats from habitat loss and fragmentation. The observed genome- and immunome-wide diversity in historical and modern jaguars reflect their recent demographic decline and challenges of local adaptation. We recommend re-evaluating evolutionarily significant units to prioritize conservation strategies, ensuring the preservation of unique genetic and adaptive diversity crucial for the species' resilience and long-term survival.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"415"},"PeriodicalIF":12.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of microprotein-coding intronic polyadenylation isoforms and function in genotoxic anticancer drug response.","authors":"Alexandre Devaux, Iris Tanaka, Quentin Fouilleul, Amélie Heneman-Masurel, Mandy Cadix, Sophie Michallet, Alina Chakraborty, Céline M Labbé, Nicolas Fontrodona, Subhadarsini Sahoo, Jean-Baptiste Claude, Marc Deloger, Pierre Gestraud, Ludovic Tessier, Hussein Mortada, Sonia Lameiras, Virginie Raynal, Sylvain Baulande, Nicolas Servant, Didier Auboeuf, Béatrice Eymin, Stéphan Vagner, Martin Dutertre","doi":"10.1186/s13059-025-03829-7","DOIUrl":"10.1186/s13059-025-03829-7","url":null,"abstract":"<p><strong>Background: </strong>Many transcript isoforms generated by intronic polyadenylation (IPA) encode isoforms of canonical proteins. Microproteins are an emerging class of small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown.</p><p><strong>Results: </strong>Here, by crossing 3'-seq, Ribo-Seq, and mass-spectrometry data, we identify 297 genes with a microprotein-coding IPA isoform terminating in a 5'UTR intron (coined miP-5'UTR-IPA isoform). By 3'-seq and long-read RNA-seq analyses in lung cancer cells treated with cisplatin, a DNA-cross-linking anticancer drug, we find that cisplatin globally favors the expression of (miP-5'UTR-)IPA isoforms relative to full-length mRNAs, mainly by decreasing the latter through an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. The cisplatin-regulated miP-5'UTR-IPA isoform in the PRKAR1B gene is translated, as it is associated with light polysome fractions and contains Ribo-Seq-supported sORFs in its alternative last exon, and the microprotein (PRKAR1B-IPA-miP2) encoded by its sORF#2 is detected by Western blot and immunofluorescence. CRISPR editing of either the IPA site or the sORF#2 initiation site leads to decreased cell growth inhibition by cisplatin and camptothecin, another genotoxic drug. Mechanistically, PRKAR1B-IPA-miP2 promotes p53 protein induction by cisplatin. Finally, 70 miP-5'UTR-IPA isoforms are detected in normal cells, and 143 are upregulated by cisplatin.</p><p><strong>Conclusions: </strong>Here, we show that IPA isoforms are a novel source of microproteins, and we reveal the novel paradigm of miP-5'UTR-IPA genes that produce both a canonical full-length mRNA and a microprotein-coding IPA isoform.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"366"},"PeriodicalIF":12.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}