Genome research最新文献

Glucocorticoid regulation of the human noncoding genome. 人类非编码基因组的糖皮质激素调控。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-16 DOI: 10.1101/gr.281820.125

Thai Tran, Robert Kwiat, Qilin Cao, Skyler Kuhn, Katherine N Howe, Manasi Gadkari, Luis M Franco

{"title":"Glucocorticoid regulation of the human noncoding genome.","authors":"Thai Tran, Robert Kwiat, Qilin Cao, Skyler Kuhn, Katherine N Howe, Manasi Gadkari, Luis M Franco","doi":"10.1101/gr.281820.125","DOIUrl":"https://doi.org/10.1101/gr.281820.125","url":null,"abstract":"Glucocorticoids (GCs) are widely used anti-inflammatory and immunosuppressive agents known to induce substantial changes in gene expression, yet their effects on noncoding RNAs such as long noncoding RNAs (lncRNAs) or microRNAs (miRNAs) remain poorly characterized. Here, we present the first comprehensive and systematic analysis of GC regulation of the noncoding genome across nine human primary cell types from both hematopoietic and nonhematopoietic lineages. In vitro GC treatment was applied to each cell type, with transcriptomic profiling (total RNA-seq and small RNA-seq) at 2 and 6 h posttreatment. We identify more than 2000 GC-responsive noncoding transcripts, including 654 annotated lncRNAs, 1376 novel lncRNAs, and 39 miRNAs. The noncoding RNA response to GCs is highly cell type dependent: 80% of GC-responsive lncRNAs and 97% of miRNAs are unique to a single cell type. Hematopoietic cells exhibit a greater magnitude of lncRNA induction compared with nonhematopoietic cells. Notably, GC treatment uncovers dozens of facultative, stimulus-dependent lncRNAs. GC-responsive transcripts span diverse lncRNA classes, with enrichment of host lncRNAs. In contrast, only a limited number of miRNAs are GC responsive. GC regulation of transcript abundance for miRNAs and their host lncRNAs appears to be independent. Our results, which are accessible through an interactive web application, establish a framework for studying how noncoding transcription contributes to physiological and clinical heterogeneity in GC responses. The newly identified GC-responsive noncoding transcripts could represent biomarkers of GC exposure, determinants of GC sensitivity or resistance, or candidate regulators of tissue-specific GC effects.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206773","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

Pangenome and transcriptomics reveal the genomic basis associated with interspecific variation of sexually dimorphic nuptial spines in moustache toads. 泛基因组学和转录组学揭示了与小胡子蟾蜍两性二型婚棘种间变异相关的基因组基础。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-16 DOI: 10.1101/gr.282034.126

Jun Li, Yan Feng, Shaodi Huang, Siyu Xie, Qingbo Ai, Chunhua Huang, Rufeng Xiong, Mian Zhao, Hua Wu

{"title":"Pangenome and transcriptomics reveal the genomic basis associated with interspecific variation of sexually dimorphic nuptial spines in moustache toads.","authors":"Jun Li, Yan Feng, Shaodi Huang, Siyu Xie, Qingbo Ai, Chunhua Huang, Rufeng Xiong, Mian Zhao, Hua Wu","doi":"10.1101/gr.282034.126","DOIUrl":"https://doi.org/10.1101/gr.282034.126","url":null,"abstract":"Sexual dimorphism is a widespread phenotypic innovation that plays a crucial role in species diversification, yet its genetic origins and evolutionary trajectories remain poorly understood in vertebrates. Leptobrachium provides a tractable system in which male moustache toads develop maxillary nuptial spines used in male-male combat, whereas closely related pseudo-moustache toads lack this trait. To investigate the evolutionary genomics of these sexually dimorphic nuptial spines, we construct a pangenome from chromosome-level assemblies of six Leptobrachium species and integrate trans-species transcriptomic analyses. We find that keratin gene expansion predated the origin of nuptial spines, potentially providing genetic material for keratinized skin innovation. Recently duplicated hair keratin genes acquired putative Hoxc13 binding sites, and promoter reporter assays confirm that Hoxc13 can activate these genes in both moustache toads and pseudo-moustache toads. Differential hoxc13 expression may therefore be more important for affecting whether duplicated hair keratin genes are recruited to develop nuptial spines. Transcriptomic comparisons further reveal maxillary skin-specific expression of genes involved in keratinocyte proliferation and differentiation, as well as melanogenesis during the formation of nuptial spines. In Leptobrachium tengchongense, which has undergone secondary loss of nuptial spines, igfbp2, a conserved gene highly expressed in keratinized skin appendages across amphibians, shows positive selection and represents a candidate associated with this evolutionary transition. Our study provides amphibian pangenome resources and highlights how gene duplication coupled with regulatory recruitment may shape the evolution of novel sexually dimorphic traits in vertebrates.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206800","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

Liver X receptors participate in the fasting response by assisting CEBPB binding to enhancers and promoting the fasting transcriptional program. 肝X受体通过协助CEBPB结合增强子和促进禁食转录程序参与禁食反应。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-16 DOI: 10.1101/gr.282119.126

Tali Gorbonos, Maria C Romero Florian, Hadar Shalev, Noga Korenfeld, Cigdem Sahin, Sarah A Shawky, Dana Goldberg, Talia Radushkevitz-Frishman, Mariana Anosov-Babi, Angela Yan, Meital Charni-Natan, Meirav Bar-Shimon, Carolyn L Cummins, Ido Goldstein

{"title":"Liver X receptors participate in the fasting response by assisting CEBPB binding to enhancers and promoting the fasting transcriptional program.","authors":"Tali Gorbonos, Maria C Romero Florian, Hadar Shalev, Noga Korenfeld, Cigdem Sahin, Sarah A Shawky, Dana Goldberg, Talia Radushkevitz-Frishman, Mariana Anosov-Babi, Angela Yan, Meital Charni-Natan, Meirav Bar-Shimon, Carolyn L Cummins, Ido Goldstein","doi":"10.1101/gr.282119.126","DOIUrl":"https://doi.org/10.1101/gr.282119.126","url":null,"abstract":"Upon fasting, a group of transcription factors (TFs) activates an extensive transcriptional program in the liver to alter hepatocyte metabolism and cope with fasting. This is achieved by TF-mediated activation of enhancers, which become more accessible, leading to gene induction. Liver X receptors alpha (NR1H3) and beta (NR1H2), collectively termed here LXRs, are important TFs known to participate in transcriptional programs in the fed state, but their role in fasting is unclear. Here, we examined the effect of LXR deletion on the transcriptional and chromatin programs activated in the fasted and fed states. We profiled the liver transcriptome and genome-wide chromatin accessibility in single-knockout mice lacking either LXR isoform and in double-knockout mice lacking both isoforms. We find that double-knockout of LXRs impairs fasting-induced genes and enhancers. Analysis of genome-wide NR1H3 binding by ChIP-seq, together with chromatin accessibility profiling by ATAC-seq, shows that NR1H3 directly binds enhancers and increases their accessibility. We find that LXRs assist the binding of CCAAT/enhancer-binding protein beta (CEBPB) to enhancers during fasting. CEBPB is a key TF regulating the fasting response, and its genome-wide binding is perturbed in the absence of LXRs. Cooperation between LXRs and CEBPB promotes fasting-dependent gene induction. These findings reveal a previously unknown role for LXRs in the fasting response, whereby LXRs bind and increase enhancer accessibility, assist CEBPB binding, and promote gene induction. This study demonstrates the complex cooperation of TFs in regulating gene expression to maintain homeostasis during fasting and places LXRs as novel regulators of the fasting response.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206749","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

Conditional diffusion for single-cell Hi-C data imputation and enhancement with scHiC-Diff. 单细胞Hi-C数据的条件扩散和scHiC-Diff增强。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-16 DOI: 10.1101/gr.281897.126

Wuhao Liu, Zhaoyu Fang, Xuyan Du, Li Tang, Min Li

{"title":"Conditional diffusion for single-cell Hi-C data imputation and enhancement with scHiC-Diff.","authors":"Wuhao Liu, Zhaoyu Fang, Xuyan Du, Li Tang, Min Li","doi":"10.1101/gr.281897.126","DOIUrl":"https://doi.org/10.1101/gr.281897.126","url":null,"abstract":"Single-cell high-throughput chromosome conformation capture (scHi-C) enables the analysis of cell-to-cell variability in three-dimensional (3D) genome organization, but its utility is severely limited by pervasive technical dropouts, leading to extremely sparse contact maps. Accurately identifying dropout events and imputing the corresponding missing chromatin contacts remains a challenging problem, as technical dropouts are confounded with genuine absences of chromatin interactions. Existing imputation and enhancement methods often rely on smoothing strategies or restrictive parametric likelihood assumptions, which may obscure fine-scale chromatin structures and cell-specific features. Here, we present scHiC-Diff, a conditional diffusion-based framework for scHi-C data imputation and enhancement. scHiC-Diff employs a forward process that progressively perturbs contact maps and a reverse denoising process that reconstructs chromatin interactions from noisy observations. To better capture long-range dependencies in complex 3D genome structures, scHi-C contact matrices are treated as masked images and modeled using a Diffusion Transformer (DiT). Across two complementary simulated datasets and three real scHi-C datasets, scHiC-Diff improves the recovery of chromatin interaction patterns and enhances downstream analyses compared with existing methods. Application to a developmental scHi-C dataset further demonstrates improved reconstruction of chromatin organization and enhanced chromatin loop detection.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206770","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

Temporal transcriptomics identifies trans-regulation by multiple lncRNAs in human iPSCs. 时间转录组学鉴定了人类iPSCs中多个lncrna的转调控。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.282389.126

Mingfeng Liu, Izabela Mamede, Sajad Sofi, Isabela T Pereira, Vishantie Dostal, Alison R S Pashos, Conor McMahon, Aneesh Waikar, George Stephenson, Thomas R Cech, John L Rinn

{"title":"Temporal transcriptomics identifies trans-regulation by multiple lncRNAs in human iPSCs.","authors":"Mingfeng Liu, Izabela Mamede, Sajad Sofi, Isabela T Pereira, Vishantie Dostal, Alison R S Pashos, Conor McMahon, Aneesh Waikar, George Stephenson, Thomas R Cech, John L Rinn","doi":"10.1101/gr.282389.126","DOIUrl":"10.1101/gr.282389.126","url":null,"abstract":"Some long noncoding RNAs (lncRNAs) are known to regulate gene expression. However, the underlying temporal dynamics of lncRNAs influencing gene and epigenetic regulation, as well as mechanisms of lncRNA regulation in trans, are less understood. To investigate this, we genetically engineer 17 doxycycline-inducible lncRNA transgenes for ectopic expression at the H11 safe harbor locus in human pluripotent stem cells (hiPSCs), and we generate high-density temporal RNA-seq and ATAC-seq profiles. Most lncRNA transgenes are induced at 2 h and maintain expression through the 96 h time course. Surprisingly, when we seek to identify gene expression changes owing to the lncRNAs, we find that the global transcriptional landscape is dominated by a strong systemic response triggered by doxycycline exposure. We rigorously define this cohort of genes as a doxycycline-responsive gene signature (DRGS). The DRGS is also present in at least 28 public data sets from dox-inducible transgene studies involving diverse cell types. Next, we determine which lncRNAs exhibit trans-regulatory events. We identify DANCR, FENDRR, LINC00667, LINC00847, LNCPRESS1, and LNCPNKY as lncRNAs that regulate specific transcript expression in trans The downstream target genes encode 53 mRNAs and 10 lncRNAs. None of the target lncRNAs alter gene expression proximal to their own loci (i.e., triggering secondary cis-effects). Surprisingly, the target genes of LINC00847 (transcribed from Chromosome 22) are substantially enriched on Chromosome 19, with a preponderance of target genes encoding RNA metabolism and RNA splicing factors. Collectively, our study provides a resource to discern artifacts in the doxycycline-inducible system and identifies temporally regulated targets of six lncRNAs for future mechanistic studies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147595","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

Decoding cell division history and lineage-resolved phenotypic patterns from single-cell barcode and transcriptomic data. 从单细胞条形码和转录组数据解码细胞分裂历史和谱系解决表型模式。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.281734.125

Xiaochen Yu, Zihao Wang, Zhenquan Zhang, Yuxin Wang, Yuting Lin, Lijun Hong, Xiaoshu Chen, Xionglei He, Jian-Rong Yang, Jiajun Zhang

{"title":"Decoding cell division history and lineage-resolved phenotypic patterns from single-cell barcode and transcriptomic data.","authors":"Xiaochen Yu, Zihao Wang, Zhenquan Zhang, Yuxin Wang, Yuting Lin, Lijun Hong, Xiaoshu Chen, Xionglei He, Jian-Rong Yang, Jiajun Zhang","doi":"10.1101/gr.281734.125","DOIUrl":"10.1101/gr.281734.125","url":null,"abstract":"The cell division tree encodes how proliferation and differentiation generate cellular diversity during multicellular development. Advances in single-cell RNA sequencing and CRISPR-based lineage tracing have enabled retrospective reconstruction of these histories at single-cell resolution. Here, we present FateScape, a statistical framework that integrates paired lineage barcodes and transcriptomic profiles to infer cell division topology and characterize depth-resolved phenotypic patterns. FateScape combines barcode consistency with transcriptome-derived state continuity through overlapping state-lineage decomposition and barcode-guided subtree integration. Here, to analyze phenotypic patterns on the inferred tree, we introduce entropy paths, which measure how cells of each state are distributed across depth-defined subtrees, and Moran's I-derived statistics for same-state autocorrelation and cross-state association. In simulations, FateScape shows robust reconstruction performance across varying mutation rates, dropout levels, sample sizes, and barcode target-site numbers. In the Caenorhabditis elegans data analysis, FateScape accurately recovers lineage topology and identifies depth-resolved state patterns, including concentrated intestinal cells and broadly distributed neuronal and glial states. In mouse embryos, FateScape quantifies distinct germ-layer patterns, including early endodermal concentration, broad ectodermal distribution across shallow-to-intermediate depths, and intermediate mesodermal distribution followed by deeper concentration. Together, FateScape provides a framework for reconstructing cell division histories and quantifying state dispersion, concentration, and tree-based association across lineage depth.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016817","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

Parental genome reprogramming drives allelic convergence while preserving parent-of-origin memory during human early embryonic development. 亲本基因组重编程驱动等位基因趋同，同时在人类早期胚胎发育过程中保留亲本起源记忆。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.281969.126

Fanqing Xu, Qian Liu, Zhengrong Du, Yuwen Xiu, Qianying Guo, Jie Qiao, Peng Yuan, Liying Yan

{"title":"Parental genome reprogramming drives allelic convergence while preserving parent-of-origin memory during human early embryonic development.","authors":"Fanqing Xu, Qian Liu, Zhengrong Du, Yuwen Xiu, Qianying Guo, Jie Qiao, Peng Yuan, Liying Yan","doi":"10.1101/gr.281969.126","DOIUrl":"https://doi.org/10.1101/gr.281969.126","url":null,"abstract":"Human sperm and oocytes carry highly distinct DNA methylation landscapes, yet parental DNA methylation ultimately converges to a largely equivalent state, raising the question of when and how the allelic DNA methylome is reprogrammed toward convergence. Here, we present an integrated allelic analysis of DNA methylation and transcriptome dynamics throughout human pre- to peri-implantation development, a stage that lays the foundation for future development. We find that oocyte-specific hypermethylated regions retain maternal-biased DNA methylation asymmetry throughout early development, whereas paternal hypermethylation at sperm-specific regions is erased after fertilization and re-established during peri-implantation. Whole-genome parental DNA methylation levels converge across all lineages at embryonic days 8 to 12, prior to gastrulation, although the timing of this equilibrium differs among genomic elements. Notably, a subset of transposable elements, including SVAs and LTR12 elements, remains persistently maternally hypermethylated. Finally, we identify parent-of-origin-biased genes involved in early human embryonic development and find that these genes are enriched for dosage-sensitive genes. We further show that epiblast-specific parental expression bias is associated with genes implicated in neurodevelopmental disorders. These findings highlight the developmental and clinical relevance of allele-specific DNA methylation and transcription regulation during the earliest stages of human development.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181053","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

Nanopore sequencing identifies high-frequency somatic structural variations in laryngeal squamous cell carcinoma genomes. 纳米孔测序鉴定喉鳞癌基因组高频体细胞结构变异。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.281046.125

Xuyan Liu, Lin Xia, Yixin Qiao, Yang Li, Yan Huang, Bingyan Yue, Xi Liang, Xin Yang, Honghui Zhang, Jiaxun Zhang, Xiao Chen, Dan Xie, Jifeng Liu

{"title":"Nanopore sequencing identifies high-frequency somatic structural variations in laryngeal squamous cell carcinoma genomes.","authors":"Xuyan Liu, Lin Xia, Yixin Qiao, Yang Li, Yan Huang, Bingyan Yue, Xi Liang, Xin Yang, Honghui Zhang, Jiaxun Zhang, Xiao Chen, Dan Xie, Jifeng Liu","doi":"10.1101/gr.281046.125","DOIUrl":"10.1101/gr.281046.125","url":null,"abstract":"Laryngeal squamous cell carcinoma (LSCC) is an aggressive cancer associated with poor quality of life. Understanding the somatic mutations in its genome is crucial for elucidating its occurrence and progression. Although somatic structural variations (SVs) have been documented in LSCC, conventional short-read sequencing lacks the sensitivity to effectively detect high-frequency SVs, variants that play a crucial role in tumorigenesis, shared across multiple samples. Here, we present SomaGauss-SV, a somatic SV detection workflow leveraging nanopore long-read sequencing data. Benchmarking against five paired tumor cell line data sets shows SomaGauss-SV consistently achieves a balanced high precision and recall. SomaGauss-SV applied to 15 paired LSCC tumor-blood samples uncovers a comprehensive SV landscape and reveals a significant positive correlation between somatic deletion burden and smoking intensity. Furthermore, a high-frequency somatic simple repeat expansion is identified in 28/39 (71.79%) of LSCC patients, which upregulates the expression of genes TP53BP2 and FBXO28 through spatial proximity. These findings underscore the potential of long-read sequencing and SomaGauss-SV for uncovering recurrent somatic SVs in LSCC, providing valuable resources for biomarker discovery.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638628","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

The divergent 3D genome landscapes of aging and neurodegenerative mouse models. 衰老和神经退行性小鼠模型的不同三维基因组景观。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.281732.125

Ekaterina Kashuk, Dmitrii Smirnov, Ekaterina Eremenko, Alexandra Tsitrina, Dmitrii Kriukov, Anastasia Golova, Shai Kaluski-Kopatch, Ekaterina Khrameeva, Debra Toiber

{"title":"The divergent 3D genome landscapes of aging and neurodegenerative mouse models.","authors":"Ekaterina Kashuk, Dmitrii Smirnov, Ekaterina Eremenko, Alexandra Tsitrina, Dmitrii Kriukov, Anastasia Golova, Shai Kaluski-Kopatch, Ekaterina Khrameeva, Debra Toiber","doi":"10.1101/gr.281732.125","DOIUrl":"https://doi.org/10.1101/gr.281732.125","url":null,"abstract":"Chromatin structure is essential for gene regulation and genome stability, as neurons must preserve their 3D genome organization throughout life. This structure gradually deteriorates with aging and is further disrupted in neurodegenerative diseases. To investigate whether aging and neurodegeneration share early chromatin changes or diverge, we perform Hi-C on cortical neurons from adult, aged, and brain-specific SIRT6-knockout (S6-KO) mice and compare them to the previously published Hi-C data sets from a CK-p25 Alzheimer's disease model stratified by γH2AX levels. All models show early features such as weakened interactions between chromosomes in expanded nuclei, A- to B-compartment shifts, and loss of architectural loops. However, aged neurons retain TAD prominence, short-range interactions, and enhancer-promoter loops, whereas pathological models showed reduced TAD prominence, shorter loops, and disorganized A-B mixing. These changes correlate with increased DNA damage. Our findings suggest that aging represents a \"primed\" state, in which chromatin regulation begins to erode, but further stressors like DNA damage are associated with progression toward neurodegenerative breakdown.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181089","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

Reconstruction of contact signals from repeated elements with Hicberg. 用Hicberg从重复元素中重建接触信号。

IF 6.3 2区生物学

Genome research Pub Date : 2026-10-13 DOI: 10.1101/gr.281770.125

Sébastien Gradit, Samuel Ortion, Pauline Larrous, Maëlys Delouis, Romain Koszul, Axel Cournac

引用次数: 0