Genome Biology最新文献

New insights into the cold tolerance of upland switchgrass by integrating a haplotype-resolved genome and multi-omics analysis 整合单倍型解决基因组和多组学分析对山地柳枝稷耐寒性的新见解

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-14 DOI: 10.1186/s13059-025-03604-8

Bingchao Wu, Dan Luo, Yuesen Yue, Haidong Yan, Min He, Xixi Ma, Bingyu Zhao, Bin Xu, Jie Zhu, Jing Wang, Jiyuan Jia, Min Sun, Zheni Xie, Xiaoshan Wang, Linkai Huang

{"title":"New insights into the cold tolerance of upland switchgrass by integrating a haplotype-resolved genome and multi-omics analysis","authors":"Bingchao Wu, Dan Luo, Yuesen Yue, Haidong Yan, Min He, Xixi Ma, Bingyu Zhao, Bin Xu, Jie Zhu, Jing Wang, Jiyuan Jia, Min Sun, Zheni Xie, Xiaoshan Wang, Linkai Huang","doi":"10.1186/s13059-025-03604-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03604-8","url":null,"abstract":"Switchgrass (Panicum virgatum L.) is a bioenergy and forage crop. Upland switchgrass exhibits superior cold tolerance compared to the lowland ecotype, but the underlying molecular mechanisms remain unclear. Here, we present a high-quality haplotype-resolved genome of the upland ecotype “Jingji31.” We then conduct multi-omics analysis to explore the mechanism underlying its cold tolerance. By comparative transcriptome analysis of the upland and lowland ecotypes, we identify many genes with ecotype-specific differential expression, particularly members of the cold-responsive (COR) gene family, under cold stress. Notably, AFB1, ATL80, HOS10, and STRS2 gene families show opposite expression changes between the two ecotypes. Based on the haplotype-resolved genome of “Jingji31,” we detect more cold-induced allele-specific expression genes in the upland ecotype than in the lowland ecotype, and these genes are significantly enriched in the COR gene family. By genome-wide association study, we detect an association signal related to the overwintering rate, which overlaps with a selective sweep region containing a cytochrome P450 gene highly expressed under cold stress. Heterologous overexpression of this gene in rice alleviates leaf chlorosis and wilting under cold stress. We also verify that expression of this gene is suppressed by a structural variation in the promoter region. Based on the high-quality haplotype-resolved genome and multi-omics analysis of upland switchgrass, we characterize candidate genes responsible for cold tolerance. This study advances our understanding of plant cold tolerance, which provides crop breeding for improved cold tolerance.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"10 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the role of RNA in regulating CTCF’s DNA binding affinity in leukemia cells 破译RNA在白血病细胞中调节CTCF DNA结合亲和力中的作用

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-12 DOI: 10.1186/s13059-025-03582-x

Judith Hyle, Wenjie Qi, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Beisi Xu, Chunliang Li

{"title":"Deciphering the role of RNA in regulating CTCF’s DNA binding affinity in leukemia cells","authors":"Judith Hyle, Wenjie Qi, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Beisi Xu, Chunliang Li","doi":"10.1186/s13059-025-03582-x","DOIUrl":"https://doi.org/10.1186/s13059-025-03582-x","url":null,"abstract":"CTCF, a highly studied transcription factor, is essential for chromatin interaction maintenance. Several independent studies report that CTCF interacts with RNAs in vitro and in cells. Yet continuous debates about the authenticity of the RNA-binding affinity of CTCF and its biological role remain in large part due to limited research techniques available, such as CLIP-seq. Here, we investigate RNA’s role in CTCF’s transcription factor function through its chromatin occupancy. To systematically explore whether RNAs affect CTCF’s ability to bind DNA, we perturb CTCF-RNA interactions by three independent approaches and examine CTCF genome occupancy by ChIP-seq. Although RNase A and triptolide treatment each affect a certain number of CTCF-binding peaks, few peaks overlap between treatment groups indicating the effect of RNA in regulating CTCF’s DNA binding affinity is variable between loci. In addition, limited transcriptional or chromatin accessibility changes occur between cells expressing wild-type CTCF or CTCF lacking the RNA binding region. Our data provide a complementary approach and in silico evidence to consider the significance of RNA affecting CTCF’s DNA binding affinity globally.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"32 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ChromActivity: integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types ChromActivity：基于不同人类细胞类型调节活性注释的综合表观基因组和功能表征分析

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-09 DOI: 10.1186/s13059-025-03579-6

Tevfik Umut Dincer, Jason Ernst

引用次数: 0

Most human DNA replication initiation is dispersed throughout the genome with only a minority within previously identified initiation zones 大多数人类DNA复制起始分散在整个基因组中，只有少数在先前确定的起始区

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-09 DOI: 10.1186/s13059-025-03591-w

Jamie T. Carrington, Rosemary H. C. Wilson, Eduardo de La Vega, Sathish Thiyagarajan, Tom Barker, Leah Catchpole, Alex Durrant, Vanda Knitlhoffer, Chris Watkins, Karim Gharbi, Conrad A. Nieduszynski

{"title":"Most human DNA replication initiation is dispersed throughout the genome with only a minority within previously identified initiation zones","authors":"Jamie T. Carrington, Rosemary H. C. Wilson, Eduardo de La Vega, Sathish Thiyagarajan, Tom Barker, Leah Catchpole, Alex Durrant, Vanda Knitlhoffer, Chris Watkins, Karim Gharbi, Conrad A. Nieduszynski","doi":"10.1186/s13059-025-03591-w","DOIUrl":"https://doi.org/10.1186/s13059-025-03591-w","url":null,"abstract":"The identification of sites of DNA replication initiation in mammalian cells has been challenging. Here, we present unbiased detection of replication initiation events in human cells using BrdU incorporation and single-molecule nanopore sequencing. Increases in BrdU incorporation allow us to measure DNA replication dynamics, including identification of replication initiation, fork direction, and termination on individual nanopore sequencing reads. Importantly, initiation and termination events are identified on single molecules with high resolution, throughout S-phase, genome-wide, and at high coverage at specific loci using targeted enrichment. We find a significant enrichment of initiation sites within the broad initiation zones identified by population-level studies. However, these focused initiation sites only account for ~ 20% of all identified replication initiation events. Most initiation events are dispersed throughout the genome and are missed by cell population approaches. This indicates that most initiation occurs at sites that, individually, are rarely used. These dispersed initiation sites contrast with the focused sites identified by population studies, in that they do not show a strong relationship to transcription or a particular epigenetic signature. We show here that single-molecule sequencing enables unbiased detection and characterization of DNA replication initiation events, including the numerous dispersed initiation events that replicate most of the human genome.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"28 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations 子宫内膜肿瘤发生涉及区分非编码体细胞突变和3d基因组改变的表观遗传可塑性

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-09 DOI: 10.1186/s13059-025-03596-5

Sebastian Gregoricchio, Aleksandar Kojic, Marlous Hoogstraat, Karianne Schuurman, Suzan Stelloo, Tesa M. Severson, Tracy A. O’Mara, Marjolein Droog, Abhishek A. Singh, Dylan M. Glubb, Lodewyk F. A. Wessels, Michiel Vermeulen, Flora E. van Leeuwen, Wilbert Zwart

{"title":"Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations","authors":"Sebastian Gregoricchio, Aleksandar Kojic, Marlous Hoogstraat, Karianne Schuurman, Suzan Stelloo, Tesa M. Severson, Tracy A. O’Mara, Marjolein Droog, Abhishek A. Singh, Dylan M. Glubb, Lodewyk F. A. Wessels, Michiel Vermeulen, Flora E. van Leeuwen, Wilbert Zwart","doi":"10.1186/s13059-025-03596-5","DOIUrl":"https://doi.org/10.1186/s13059-025-03596-5","url":null,"abstract":"The incidence and mortality of endometrial cancer (EC) is on the rise. Eighty-five percent of ECs depend on estrogen receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors. We generate epigenomics, transcriptomics, and Hi-C datastreams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in 3D genome organization that lead to a gain of tumor-specific enhancer activity during EC development. Integration with endometrial cancer risk single-nucleotide polymorphisms and whole-genome sequencing data from primary tumors and metastatic samples reveals a striking enrichment of risk variants and non-coding somatic mutations at tumor-enriched ERα sites. Through machine learning-based predictions and interaction proteomics analyses, we identify an enhancer mutation which alters 3D genome conformation, impairing recruitment of the transcriptional repressor EHMT2/G9a/KMT1C, thereby alleviating transcriptional repression of ESR1 in EC. In summary, we identify a complex genomic-epigenomic interplay in EC development and progression, altering 3D genome organization to enhance expression of the critical driver ERα.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"11 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish 母源基因的亲本调控决定了鱼类的神经发育和行为

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-09 DOI: 10.1186/s13059-025-03600-y

Antoine Emile Clément, Constance Merdrignac, Sergi Roig Puiggros, Dorine Sévère, Aurélien Brionne, Thomas Lafond, Thaovi Nguyen, Jérôme Montfort, Cervin Guyomar, Alexandra Dauvé, Amaury Herpin, Denis Jabaudon, Violaine Colson, Florent Murat, Julien Bobe

{"title":"Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish","authors":"Antoine Emile Clément, Constance Merdrignac, Sergi Roig Puiggros, Dorine Sévère, Aurélien Brionne, Thomas Lafond, Thaovi Nguyen, Jérôme Montfort, Cervin Guyomar, Alexandra Dauvé, Amaury Herpin, Denis Jabaudon, Violaine Colson, Florent Murat, Julien Bobe","doi":"10.1186/s13059-025-03600-y","DOIUrl":"https://doi.org/10.1186/s13059-025-03600-y","url":null,"abstract":"Parental experience can influence progeny behavior through gamete-mediated non-genetic inheritance, that is, mechanisms that do not involve changes in inherited DNA sequence. However, underlying mechanisms remain poorly understood in vertebrates, especially for maternal effects. Here, we use the medaka, a model fish species, to investigate the role of auts2a, the ortholog of human AUTS2, a gene repressed in the fish oocyte following maternal stress and associated with neurodevelopmental disorders. We show that auts2a expression in the oocyte influences long-term progeny behavior, including anxiety-like behavior and environment recognition capabilities. Using single-nuclei RNA-sequencing, we reveal that maternal auts2a influences gene expression in neural cell populations during neurodevelopment. We also show that maternal auts2a knock-out triggers differences in maternally inherited factors, including early embryonic transcriptional and post-transcriptional regulators. Together, our results reveal the unsuspected role of an autism-related gene expressed in the mother’s oocyte in shaping progeny neurodevelopment and behavior. Finally, we report that auts2a/AUTS2 is part of a group of evolutionarily conserved genes associated with human neurodevelopmental disorders and expressed in oocytes across species, from fish to mammals. These findings raise important questions about their potential role in the non-genetic regulation of progeny neurodevelopment and behavior in vertebrates.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"49 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-read sequencing reveals novel isoform-specific eQTLs and regulatory mechanisms of isoform expression in human B cells 长读测序揭示了人类B细胞中新的异构体特异性eqtl和异构体表达的调控机制

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03583-w

Yuya Nagura, Mihoko Shimada, Ryoji Kuribayashi, Ko Ikemoto, Hiroki Kiyose, Arisa Igarashi, Tadashi Kaname, Motoko Unoki, Akihiro Fujimoto

{"title":"Long-read sequencing reveals novel isoform-specific eQTLs and regulatory mechanisms of isoform expression in human B cells","authors":"Yuya Nagura, Mihoko Shimada, Ryoji Kuribayashi, Ko Ikemoto, Hiroki Kiyose, Arisa Igarashi, Tadashi Kaname, Motoko Unoki, Akihiro Fujimoto","doi":"10.1186/s13059-025-03583-w","DOIUrl":"https://doi.org/10.1186/s13059-025-03583-w","url":null,"abstract":"Genetic variations linked to changes in gene expression are known as expression quantitative loci (eQTLs). The identification of eQTLs helps to understand the mechanisms governing gene expression. However, prior studies have primarily utilized short-read sequencing techniques, and the analysis of eQTLs on isoforms has been relatively limited. In this study, we employ long-read sequencing technology (Oxford Nanopore) on B cells from 67 healthy Japanese individuals to explore genetic variations associated with isoform expression levels, referred to as isoform eQTLs (ieQTLs). Our analysis reveals 17,119 ieQTLs, with 70.6% remaining undetected by a gene-level analysis. Additionally, we identify ieQTLs that have significantly different effects on isoform expression levels within a gene. A functional feature analysis demonstrates a significant enrichment of ieQTLs at splice sites and specific histone marks, such as H3K36me3, H3K4me1, H3K4me3, and H3K79me2. Through an experimental validation using genome editing, we observe that a distant genomic region can modulate isoform-specific expression. Moreover, an ieQTL analysis and minigene splicing assays unveils functionally crucial variants in splicing that splicing prediction software did not assign a high prediction score. A comparison with GWAS data reveals a higher number of colocalizations between ieQTLs and GWAS findings compared to gene eQTLs. These findings highlight the substantial contribution of ieQTLs identified through long-read analysis in our understanding of the functional implications of genetic variations and the regulatory mechanisms governing isoforms.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"25 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenome profiling reveals distinctive regulatory features and cis-regulatory elements in pepper 表观基因组分析揭示了辣椒独特的调控特征和顺式调控元件

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03595-6

Hongji Yang, Guorong Yu, Zhidong Lv, Tonghui Li, Xi Wang, Ying Fu, Zhangsheng Zhu, Guangjun Guo, Hang He, Ming Wang, Guochen Qin, Feng Liu, Zhenhui Zhong, Yan Xue

{"title":"Epigenome profiling reveals distinctive regulatory features and cis-regulatory elements in pepper","authors":"Hongji Yang, Guorong Yu, Zhidong Lv, Tonghui Li, Xi Wang, Ying Fu, Zhangsheng Zhu, Guangjun Guo, Hang He, Ming Wang, Guochen Qin, Feng Liu, Zhenhui Zhong, Yan Xue","doi":"10.1186/s13059-025-03595-6","DOIUrl":"https://doi.org/10.1186/s13059-025-03595-6","url":null,"abstract":"Pepper (Capsicum annuum) is one of the earliest and most widely cultivated vegetable crops worldwide. While the large and complex genome of pepper severely hampered the understanding of its functional genome, it also indicates a rich yet unexplored reservoir of regulatory elements (REs). In fact, variations in the REs represent a major driving force in evolution and domestication in both plants and animals. However, identification of the REs remains difficult especially for plants with complex genomes. Here, we present a comprehensive epigenomic landscape of Capsicum annuum, Zhangshugang (ST-8), including chromatin accessibility, histone modifications, DNA methylation, and transcriptome. We also develop comparative crosslinked immunoprecipitation mass spectrometry to reveal the proteome associated with certain chromatin features. Through integrated analysis of these epigenetic features, we profile promoters and enhancers involved in development, heat stress and cucumber mosaic virus challenges. We generate stress responsive expression networks composed of potential transcription activators and their target genes. Through population genetics analysis, we demonstrate that some regulatory elements show lower nucleotide diversity compare to other genomic regions during evolution. We demonstrate that variations in the REs may contribute to more diversified and agronomically desired phenotypes. Our study provides a foundation not only for studying gene regulation, but also for targeted genetic and epigenetic manipulation for pepper improvement.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"12 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Determining the functional relationship between epigenetic and physical chromatin domains in Drosophila 确定果蝇表观遗传和物理染色质结构域之间的功能关系

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03587-6

Sandrine Denaud, Gonzalo Sabarís, Marco Di Stefano, Giorgio-Lucio Papadopoulos, Bernd Schuettengruber, Giacomo Cavalli

引用次数: 0

ONTraC characterizes spatially continuous variations of tissue microenvironment through niche trajectory analysis ONTraC通过生态位轨迹分析来表征组织微环境的空间连续变化

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03588-5

Wen Wang, Shiwei Zheng, Sujung Crystal Shin, Joselyn Cristina Chávez-Fuentes, Guo-Cheng Yuan

引用次数: 0