Genome research最新文献_第7页

Dynamic barriers modulate cohesin positioning and genome folding at fixed occupancy 动态屏障调节内聚定位和基因组折叠在固定占用

IF 7 2区生物学

Genome research Pub Date : 2025-07-08 DOI: 10.1101/gr.280108.124

Hadi Rahmaninejad, Yao Xiao, Maxime M.C. Tortora, Geoffrey Fudenberg

{"title":"Dynamic barriers modulate cohesin positioning and genome folding at fixed occupancy","authors":"Hadi Rahmaninejad, Yao Xiao, Maxime M.C. Tortora, Geoffrey Fudenberg","doi":"10.1101/gr.280108.124","DOIUrl":"https://doi.org/10.1101/gr.280108.124","url":null,"abstract":"In mammalian interphase cells, genomes are folded by cohesin loop extrusion limited by directional CTCF barriers. This process enriches cohesin at barriers, isolates neighboring topologically associating domains, and elevates contact frequency between convergent CTCF barriers across the genome. However, recent in vivo measurements present a puzzle: reported CTCF residence times on chromatin are in the range of a few minutes, whereas cohesin lifetimes are much longer. Can the observed features of genome folding result from relatively transient barriers? To address this question, we develop a dynamic barrier model, where CTCF sites switch between bound and unbound states. Using this model, we investigate how barrier dynamics would impact observables for a range of experimental genomic and imaging data sets, including ChIP-seq, Hi-C, and microscopy. We find the interplay of CTCF and cohesin binding timescales influence the strength of each of these features, leaving a signature of barrier dynamics even in the population-averaged snapshots offered by genomic data sets. First, in addition to barrier occupancy, barrier bound times are crucial for instructing features of genome folding. Second, the ratio of boundary to extruder lifetime greatly alters simulated ChIP-seq and simulated Hi-C. Third, large-scale changes in chromosome morphology observed experimentally after increasing extruder lifetime require dynamic barriers. By integrating multiple sources of experimental data, our biophysical model argues that CTCF barrier bound times effectively approach those of cohesin extruder lifetimes. Together, we demonstrate how models that are informed by biophysically measured protein dynamics broaden our understanding of genome folding.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"21 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Batch correction methods used in single-cell RNA sequencing analyses are often poorly calibrated 单细胞RNA测序分析中使用的批量校正方法往往校准不良

IF 7 2区生物学

Genome research Pub Date : 2025-07-07 DOI: 10.1101/gr.279886.124

Sindri Emmanúel Antonsson, Páll Melsted

{"title":"Batch correction methods used in single-cell RNA sequencing analyses are often poorly calibrated","authors":"Sindri Emmanúel Antonsson, Páll Melsted","doi":"10.1101/gr.279886.124","DOIUrl":"https://doi.org/10.1101/gr.279886.124","url":null,"abstract":"As the number of experiments that employ single-cell RNA sequencing (scRNA-seq) grows, it opens up the possibility of combining results across experiments or processing cells from the same experiment assayed in separate sequencing runs. The gain in the number of cells that can be compared comes at the cost of batch effects that may be present. Several methods have been proposed to combat this for scRNA-seq data sets. We compare eight widely used methods used for batch correction of scRNA-seq data sets. We present a novel approach to measure the degree to which the methods alter the data in the process of batch correction, both at the fine scale, comparing distances between cells, as well as measuring effects observed across clusters of cells. We demonstrate that many of the published methods are poorly calibrated in the sense that the process of correction creates measurable artifacts in the data. In particular, MNN, SCVI, and LIGER perform poorly in our tests, often altering the data considerably. Batch correction with Combat, ComBat-seq, BBKNN, and Seurat introduces artifacts that could be detected in our setup. However, we find that Harmony is the only method that consistently performs well in all the testing methodology we present. Therefore, Harmony is the only method we recommend using when performing batch correction of scRNA-seq data.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"21 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

QuadST identifies cell-cell interaction-changed genes in spatially resolved transcriptomics data QuadST在空间解析转录组学数据中识别细胞-细胞相互作用改变的基因

IF 7 2区生物学

Genome research Pub Date : 2025-06-23 DOI: 10.1101/gr.279859.124

Xiaoyu Song, Yuqing Shang, Michelle Ehrlich, Panos Roussos, Guo-Cheng Yuan, Pei Wang

引用次数: 0

Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes Wnt信号激活诱导CTCF结合并在靶基因的顺式调控元件上形成环

IF 7 2区生物学

Genome research Pub Date : 2025-06-23 DOI: 10.1101/gr.279684.124

Anna Nordin, Chaitali Chakraborty, Mattias Jonasson, Orgena Dano, Gianluca Zambanini, Pierfrancesco Pagella, Silvia Remeseiro, Claudio Cantu

{"title":"Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes","authors":"Anna Nordin, Chaitali Chakraborty, Mattias Jonasson, Orgena Dano, Gianluca Zambanini, Pierfrancesco Pagella, Silvia Remeseiro, Claudio Cantu","doi":"10.1101/gr.279684.124","DOIUrl":"https://doi.org/10.1101/gr.279684.124","url":null,"abstract":"Wnt signaling plays a pivotal role during development and homeostasis. Upon pathway activation, CTNNB1 (also known as beta-catenin) drives the expression of target genes from regulatory regions bound by TCF/LEF transcription factors. Gene regulation, however, entails the interplay between sequence information and 3D genome structure, yet the impact of Wnt signaling on genome structure has been poorly explored. Here we investigate how Wnt signaling influences CTCF and cohesin, key regulators of 3D genome organization. We identify a series of novel CTCF binding sites that emerge upon Wnt stimulation: CTCF redistributions under Wnt (RUW). RUW sites are characterized by CTCF, cohesin and TCF/LEF occupancy and are dependent on beta-catenin. Beta-catenin and CTCF colocalize upon pathway activation, and disruption of selected binding sites perturbs target gene regulation. Moreover, Wnt signaling reorganizes the 3D genome as evidenced by genome-wide alterations in CTCF-bound loops. This work reveals a previously unexplored role for CTCF in the regulation of Wnt signaling.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"243 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multi-tissue single-nucleus RNA-seq reveals cell type-specific regulatory patterns of alternative polyadenylation in pigs 多组织单核RNA-seq揭示了猪选择性聚腺苷酸化的细胞类型特异性调控模式

IF 7 2区生物学

Genome research Pub Date : 2025-06-16 DOI: 10.1101/gr.280095.124

Qiuhan Wen, Zhen Wang, Qi Bao, Tianli Ding, Haihan Zhang, Jianbo Li, Zhuang Liu, Jieping Huang, Guoqiang Yi

{"title":"Multi-tissue single-nucleus RNA-seq reveals cell type-specific regulatory patterns of alternative polyadenylation in pigs","authors":"Qiuhan Wen, Zhen Wang, Qi Bao, Tianli Ding, Haihan Zhang, Jianbo Li, Zhuang Liu, Jieping Huang, Guoqiang Yi","doi":"10.1101/gr.280095.124","DOIUrl":"https://doi.org/10.1101/gr.280095.124","url":null,"abstract":"As an important post-transcriptional modification mechanism, alternative polyadenylation (APA) plays a crucial role in gene regulation and phenotypic diversity. While extensive studies have explored the global APA landscape using bulk RNA-seq data, in-depth analyses of APA events at the single-cell level remain limited - particularly in farm animals. In this study, we constructed a comprehensive APA atlas for 261 cell types across 19 porcine tissues based on single-nucleus RNA sequencing (snRNA-seq) data. This analysis revealed tissue- and cell type-specific patterns of APA. We found that many genes displayed a clear correlation between the average length of 3' untranslated regions (3'UTRs) and expression levels in various cell types, with most showing a negative correlation. Early cell types within the developmental lineage, such as spermatogonia and satellite cells, displayed longer 3'UTRs, especially for spermatogenesis, where 3'UTR lengths showed significant decreasing trends along the differentiation trajectory. Notably, we identified that variable 3'UTR lengths in the CD47 and GPD1 genes might be critical regulators during spermatogenesis and myogenesis, respectively, potentially through modulation of RNA-binding protein and miRNA binding sites. Furthermore, the SNP rs323354626, located in the 3'UTR of the CD47 gene, significantly impacts gene splicing and is strongly associated with reproductive phenotypes. Additionally, we observed that neuronal cells generally possess longer 3'UTRs – a pattern conserved across humans, mice, fruit flies, and pigs. Together, these findings enrich the single-cell atlas of pigs by adding a layer of post-transcriptional regulation to the existing gene expression data, highlighting the significant role of cell type-specific 3'UTR lengths in cell commitment and complex trait regulation.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"21 1","pages":"gr.280095.124"},"PeriodicalIF":7.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Accurate short-read alignment through r-index-based pangenome indexing 通过基于r索引的泛基因组索引进行精确的短读比对

IF 7 2区生物学

Genome research Pub Date : 2025-06-12 DOI: 10.1101/gr.279858.124

Rahul Varki, Massimiliano Rossi, Eddie Ferro, Marco Oliva, Erik Garrison, Ben Langmead, Christina Boucher

{"title":"Accurate short-read alignment through r-index-based pangenome indexing","authors":"Rahul Varki, Massimiliano Rossi, Eddie Ferro, Marco Oliva, Erik Garrison, Ben Langmead, Christina Boucher","doi":"10.1101/gr.279858.124","DOIUrl":"https://doi.org/10.1101/gr.279858.124","url":null,"abstract":"Aligning to a linear reference genome can result in a higher percentage of reads going unmapped or being incorrectly mapped owing to variations not captured by the reference, otherwise known as reference bias. Recently, in efforts to mitigate reference bias, there has been a movement to switch to using pangenomes, a collection of genomes, as the reference. In this paper, we introduce Moni-align, the first short-read pangenome aligner built on the r-index, a variation of the classical FM-index that can index collections of genomes in O(r)-space, where r is the number of runs in the Burrows–Wheeler transform. Moni-align uses a seed-and-extend strategy for aligning reads, utilizing maximal exact matches as seeds, which can be efficiently obtained with the r-index. Using both simulated and real short-read data sets, we demonstrate that Moni-align achieves alignment accuracy comparable to vg map and vg giraffe, the leading pangenome aligners. Although currently best suited for aligning to localized pangenomes owing to computational constraints, Moni-align offers a robust foundation for future optimizations that could further broaden its applicability.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"22 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts 乳腺癌中esr1驱动增强子的综合功能注释揭示了独立于基因组和表观基因组背景的分层活性

IF 7 2区生物学

Genome research Pub Date : 2025-06-10 DOI: 10.1101/gr.280320.124

Yanis Zekri, Sebastian Gregoricchio, Elif Yapıcı, Chia-Chi Flora Huang, Tunç Morova, Umut Berkay Altıntaş, Gozde Korkmaz, Nathan A. Lack, Wilbert Zwart

{"title":"Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts","authors":"Yanis Zekri, Sebastian Gregoricchio, Elif Yapıcı, Chia-Chi Flora Huang, Tunç Morova, Umut Berkay Altıntaş, Gozde Korkmaz, Nathan A. Lack, Wilbert Zwart","doi":"10.1101/gr.280320.124","DOIUrl":"https://doi.org/10.1101/gr.280320.124","url":null,"abstract":"Estrogen receptor 1 (ESR1; also known as ERα, encoded by ESR1 gene) is the driving transcription factor in breast cancer development and progression. ESR1 genomic action is thought to operate under tight epigenetic control, with its chromatin binding and subsequent transcriptional output heavily reliant on the pioneer transcription factor FOXA1, which renders chromatin accessible for ESR1 binding. However, the exact contribution of the epigenome to selective enhancer activation by ESR1 remains to be fully elucidated. To address this, we employ a massively parallel reporter assay to profile 7576 individual ESR1 binding sites for hormone responsiveness. Only a minority of ESR1-occupied enhancers exhibit hormone-induced activity. These findings are confirmed by genomic data in situ, indicating that enhancer activation within a chromatinized context is robustly captured in a plasmid-based reporter assay. In silico integration of our findings with publicly available functional genomics data sets from breast cancer cell lines and tumor samples reveal distinct transcription complex compositions, 3D genome contexts, and regulatory dynamics associated with different classes of ESR1 binding sites. Overall, our results establish a comprehensive framework to highlight and elucidate the molecular basis underlying ESR1 genomic heterogeneity and its contribution to breast cancer biology and clinical outcomes.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"47 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells 基于ipsc的47，xyy Jacobs综合征模型揭示了与雄性X非整倍体细胞共有的DNA甲基化无关的转录失调

IF 7 2区生物学

Genome research Pub Date : 2025-06-10 DOI: 10.1101/gr.279716.124

Veronica Astro, Kelly Yojanna Cardona-Londoño, Lorena Viridiana Cortés-Medina, Rawan Alghamdi, Gustavo Ramírez-Calderón, Fotios Kefalas, Jair Dilmé-Capó, Santiago Radío, Antonio Adamo

{"title":"An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells","authors":"Veronica Astro, Kelly Yojanna Cardona-Londoño, Lorena Viridiana Cortés-Medina, Rawan Alghamdi, Gustavo Ramírez-Calderón, Fotios Kefalas, Jair Dilmé-Capó, Santiago Radío, Antonio Adamo","doi":"10.1101/gr.279716.124","DOIUrl":"https://doi.org/10.1101/gr.279716.124","url":null,"abstract":"Jacobs (JS) and Klinefelter (KS) syndromes, carrying 47,XYY and 47,XXY chromosomes, respectively, are the most prevalent sex-chromosome aneuploidies in males. JS and KS patients share several clinical features, including sterility, hormonal deficits, neurocognitive delay, and skeletal-muscle defects, although the penetrance of these traits in the two syndromes varies. Despite the high incidence, the molecular mechanisms underlying the clinical manifestations in sex aneuploid male patients are still elusive. In this study, we characterize the inaugural cohort of 47,XYY human induced pluripotent stem cells (iPSCs). We perform a comprehensive transcriptional analysis, including 47,XYY and 46,XY primary fibroblasts, iPSCs, and neural stem cells (NSCs), alongside a comparative analysis of 47,XYY and 47,XXY fibroblasts and iPSC transcriptomes. We reveal a transcriptional feedback mechanism tuning non-PAR X Chromosome gene (NPX) homologs in Y supernumerary cells, a phenomenon not detected in X aneuploid male iPSCs. By ectopically modulating the expression of selected NPY genes, we demonstrate a transcriptional link between the UTY–KDM6A gene pair. Furthermore, our analyses identify a shared transcriptomic signature between JS and KS, discernible already at the iPSC stage, with a notable enrichment for processes related to neurological functions. This transcriptomic convergence underscores potential commonalities in the molecular pathways underpinning the pathophysiology of male sex-chromosome aneuploidies. Finally, through genome-wide DNA methylation profiling of JS iPSCs, we demonstrate that a supernumerary Y Chromosome only minimally impacts the methylation status of 47,XYY cells at the pluripotent stage. Our work reveals critical transcriptional feedback mechanisms and shared gene expression signatures in male sex-chromosome aneuploidies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"13 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Developmental transcriptomics in Pristionchus reveals the environmental responsiveness of a plasticity gene-regulatory network 发育转录组学揭示了一个可塑性基因调控网络的环境响应性

IF 7 2区生物学

Genome research Pub Date : 2025-06-09 DOI: 10.1101/gr.279783.124

Shelley Reich, Tobias Loschko, Julie Jung, Samantha Nestel, Ralf J. Sommer, Michael S. Werner

{"title":"Developmental transcriptomics in Pristionchus reveals the environmental responsiveness of a plasticity gene-regulatory network","authors":"Shelley Reich, Tobias Loschko, Julie Jung, Samantha Nestel, Ralf J. Sommer, Michael S. Werner","doi":"10.1101/gr.279783.124","DOIUrl":"https://doi.org/10.1101/gr.279783.124","url":null,"abstract":"Developmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. Although significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematode Pristionchus pacificus has culminated in the identification of more than 30 genes that affect mouth form. We also recently reported the critical window of environmental sensitivity and therefore have clear expectations for when differential gene expression should matter. Here, we collated existing data into a gene-regulatory network (GRN) and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mutants to assess the regulatory logic of mouth-form plasticity. We find that only two genes in the GRN (eud-1 and seud-1/sult-1) are sensitive to the environment during the critical window. The time points of their sensitivity differ, suggesting that they act as sequential checkpoints. Additionally, seud-1/sult-1 is differentially expressed across strains and species with different mouth-form biases, highlighting the potential role of switch-gene regulation in the evolution of plasticity. We also observe temporal constraint upon the transcriptional effects of mutating the GRN and reveal unexpected feedback between mouth-form genes. Finally, a comprehensive analysis of all samples identifies metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene expression comparisons across development in up to 14 different conditions. Collectively, our results divide the GRN for mouth-form plasticity into environmentally sensitive switch genes and downstream genes that execute the decision.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"17 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding 炎症反应元件的多物种分析揭示了转座元件对NF-kB结合的古老和谱系特异性贡献

IF 7 2区生物学

Genome research Pub Date : 2025-06-06 DOI: 10.1101/gr.280357.124

Liangxi Wang, Tiegh Taylor, Kumaragurubaran Rathnakumar, Nadiya Khyzha, Minggao Liang, Azad Alizada, Laura F. Campitelli, Sara E. Pour, Zain M. Patel, Lina Antounians, Ian C. Tobias, Huayun Hou, Timothy R. Hughes, Sushmita Roy, Jennifer A. Mitchell, Jason E. Fish, Michael D. Wilson

{"title":"Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding","authors":"Liangxi Wang, Tiegh Taylor, Kumaragurubaran Rathnakumar, Nadiya Khyzha, Minggao Liang, Azad Alizada, Laura F. Campitelli, Sara E. Pour, Zain M. Patel, Lina Antounians, Ian C. Tobias, Huayun Hou, Timothy R. Hughes, Sushmita Roy, Jennifer A. Mitchell, Jason E. Fish, Michael D. Wilson","doi":"10.1101/gr.280357.124","DOIUrl":"https://doi.org/10.1101/gr.280357.124","url":null,"abstract":"Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we performed a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse, and cow, we find that 55 TE subfamilies are associated with RELA-bound regions, many of which reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA-bound regions in cow. By comparing RELA binding data across species, we also find several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we find human RELA-bound MER81 instances are enriched for the interferon gamma pathway and demonstrate that one RELA-bound MER81 element can control the TNF-induced expression of interferon gamma receptor 2 (IFNGR2). Using ancestral reconstructions, we find that RELA containing MER81 instances rapidly decayed during early primate evolution (>50 million years ago [MYA]) before stabilizing since the separation of Old World monkeys (<50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-kB regulatory networks.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"40 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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