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The dynamics of chromatin conformation involve continuous and reversible changes within the nucleus of a cell, which participate in regulating processes such as gene expression, DNA replication, and damage repair. Here, SEE is introduced, an artificial intelligence (AI) method that utilizes autoencoder and transformer techniques to analyze chromatin dynamics using single-cell RNA sequencing data and a limited number of single-cell Hi-C maps. SEE is employed to investigate chromatin dynamics across different scales, enabling the detection of (i) rearrangements in topologically associating domains (TADs), and (ii) oscillations in chromatin interactions at gene loci. Additionally, SEE facilitates the interpretation of disease-associated single-nucleotide polymorphisms (SNPs) by leveraging the dynamic features of chromatin conformation. Overall, SEE offers a single-cell, high-resolution approach to analyzing chromatin dynamics in both developmental and disease contexts.
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http://dx.doi.org/10.1002/advs.202406413 | DOI Listing |
STAR Protoc
September 2025
College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, China. Electronic address:
High-throughput chromosome conformation capture (Hi-C) provides genome-wide insights into chromatin interactions within the three-dimensional structure of the nucleus, making it a powerful tool for studying genome architecture. Here, we provide a modified in situ Hi-C protocol for small cell numbers, utilizing 50-100 embryonic cells at the 8-cell stage to investigate chromatin organization during bovine early embryonic development. This protocol overcomes the challenges of limited sample availability and offers valuable insights into chromatin dynamics during bovine early embryogenesis.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.
View Article and Find Full Text PDFJBMR Plus
October 2025
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
Genome-wide association studies (GWAS) relevant to osteoporosis have identified hundreds of loci; however, understanding how these variants influence the phenotype is complicated because most reside in non-coding DNA sequence that serves as transcriptional enhancers and repressors. To advance knowledge on these regulatory elements in osteoclasts (OCs), we performed Micro-C analysis, which informs on the genome topology of these cells and integrated the results with transcriptome and GWAS data to further define loci linked to BMD. Using blood cells isolated from 4 healthy participants aged 31-61 yr, we cultured OC in vitro and generated a Micro-C chromatin conformation capture dataset.
View Article and Find Full Text PDFClin Oncol (R Coll Radiol)
August 2025
Pharmacy College, Al-Farahidi University, Baghdad, Iraq.
Glioblastoma (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterised by profound genetic, epigenetic, and phenotypic heterogeneity. Recent advancements in high-resolution genome mapping have unveiled the critical role of three-dimensional (3D) chromatin architecture-encompassing chromatin loops, topologically associating domains, and enhancer-promoter interactions-in driving GBM tumourigenesis and therapy resistance. This review summarises recent insights into the mechanistic contribution of 3D genome reorganisation in sustaining oncogenic transcriptional programs, promoting intratumoural heterogeneity, and facilitating adaptive resistance.
View Article and Find Full Text PDFGenome Biol
September 2025
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Background: DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in guanine-rich DNA sequences and play important roles in modulating biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling allows global mapping of endogenous G4 formation.
Results: Here in this study, we map the G4 landscapes in adult skeletal muscle stem cells (MuSCs), which are essential for injury-induced muscle regeneration.