{"title":"Genome-wide modeling of DNA replication in space and time confirms the emergence of replication specific patterns in vivo in eukaryotes.","authors":"Dario D'Asaro, Jean-Michel Arbona, Vinciane Piveteau, Aurèle Piazza, Cédric Vaillant, Daniel Jost","doi":"10.1186/s13059-025-03872-4","DOIUrl":"10.1186/s13059-025-03872-4","url":null,"abstract":"","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"26 1","pages":"431"},"PeriodicalIF":12.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811698","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}
Pub Date : 2025-12-20DOI: 10.1186/s13059-025-03875-1
Verena Mutzel, Till Schwämmle, Svearike Oeverdieck, Lucija Librenjak, Benedikt Boesen, Melissa Bothe, Rutger A F Gjaltema, Ilona Dunkel, Gemma Noviello, Edda G Schulz
Background: 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.
Results: 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.
Conclusions: 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.
{"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}
Pub Date : 2025-12-15DOI: 10.1186/s13059-025-03895-x
Yuanyuan Yu, Zhi Xie
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.
{"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}
Pub Date : 2025-12-09DOI: 10.1186/s13059-025-03891-1
Rubén Barrios, Montserrat Vega, Rebeca Gracia-Domingo, Susanna Boronat, Sarela García-Santamarina, Jason C Tanny, José Ayté, Elena Hidalgo
{"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}
Pub Date : 2025-12-09DOI: 10.1186/s13059-025-03884-0
Xiaocai Xu, Manuel Neumann, Frederic Carew, Peilin Chen, Caroline Braeuning, Chloe Zubieta, Jose M Muino, Cezary Smaczniak, Kerstin Kaufmann
{"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}
Pub Date : 2025-12-08DOI: 10.1186/s13059-025-03892-0
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
{"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}
Pub Date : 2025-12-08DOI: 10.1186/s13059-025-03880-4
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
{"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}
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