Genetic factors mediating long-range enhancer–promoter communication in mammalian development

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 90, С. 102282 - 102282

Опубликована: Ноя. 22, 2024

Язык: Английский

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Liquid condensates: a new barrier to loop extrusion?

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Фев. 20, 2025

Liquid–liquid phase separation (LLPS), driven by dynamic, low-affinity multivalent interactions of proteins and RNA, results in the formation macromolecular condensates on chromatin. These structures are likely to provide high local concentrations effector factors responsible for various processes including transcriptional regulation DNA repair. In particular, enhancers, super-enhancers, promoters serve as platforms condensate assembly. current paradigm, enhancer-promoter (EP) interaction could be interpreted a result enhancer- promoter-based contact/fusion. There is increasing evidence that spatial juxtaposition enhancers provided loop extrusion (LE) SMC complexes. Here, we propose may act barriers LE, thereby contributing nuclear contacts between regulatory genomic elements.

Язык: Английский

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The establishment of the 3D genome structure during zygotic genome activation

Annals of the New York Academy of Sciences, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract During zygotic genome activation (ZGA) and early development, hierarchical levels of chromatin structure undergo remarkable perturbations: changes in the nuclear‐to‐cytoplasmic ratio various components; accessibility; histone exchange; formation 3D structures such as loops, topologically associated domains, compartments. Here, we review peculiarities, variability, emergence structural features during ZGA different organisms. Focusing on newly found called fountains , describe prerequisites for cohesin loading DNA possible mechanisms organization development. Fountains resulting from asymmetric bidirectional extrusion spread cohesin‐loading points a CTCF‐independent manner. We discuss that may not possess specific functions, unlike conventional structures, could be other biological processes where occurs.

Язык: Английский

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Identification of a Highly Conserved Region Critical for the Functionality of the Cp190 Protein in Drosophila melanogaster

Doklady Biochemistry and Biophysics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Язык: Английский

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ProOvErlap: Assessing feature proximity/overlap and testing statistical significance from genomic intervals

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 110209 - 110209

Опубликована: Май 1, 2025

Feature overlap is a critical concept in bioinformatics and occurs when two genomic intervals, usually represented as BED files, are located the same regions. Instead, feature proximity refers to spatial of elements. For example, promoters typically or close genes they regulate. Overlap also important epigenetic studies. Here, regions enriched for specific modifications accessible chromatin can elucidate complex molecular phenotypes. Consequently, ability analyze interpret essential understanding biological processes that contribute given phenotype. To address this need, we present computational method capable analyzing data format. This aims quantitatively assess degree between features determine statistical significance these events context non-parametric randomization test. The aim understand whether observed state differs from what would be expected by chance. designed easy use, requiring only single command line run, allowing straightforward analysis. It provides clear visualizations publication-quality figures. In conclusion, study highlights importance studies presents improve systematic assessment interpretation features. A new resource identifying biologically significant interactions both healthy disease states.

Язык: Английский

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Phase Separation in Chromatin Organization and Human Diseases

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5156 - 5156

Опубликована: Май 28, 2025

Understanding how the genome is organized into multi-level chromatin structures within cells and these regulate gene transcription influencing animal development human diseases has long been a major goal in genetics cell biology. Recent evidence suggests that structure formation remodeling regulated not only by loop extrusion but also phase-separated condensates. Here, we discuss recent findings on mechanisms of organization mediated phase separation, with focus roles condensates structural dysregulation diseases. Indeed, mechanistic revelations herald promising therapeutic strategies targeting condensates—leveraging their intrinsic biophysical susceptibilities to restore dysregulated aberrant separation.

Язык: Английский

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Understanding fundamental principles of enhancer biology at a model locus

BioEssays, Год журнала: 2023, Номер 45(10)

Опубликована: Июль 5, 2023

Abstract Despite ever‐increasing accumulation of genomic data, the fundamental question how individual genes are switched on during development, lineage‐specification and differentiation is not fully answered. It widely accepted that this involves interaction between at least three regulatory elements: enhancers, promoters insulators. Enhancers contain transcription factor binding sites which bound by factors (TFs) co‐factors expressed cell fate decisions maintain imposed patterns activation, in part, via their epigenetic modification. This information transferred from enhancers to cognate often coming into close physical proximity form a ‘transcriptional hub’ containing high concentration TFs co‐factors. The mechanisms underlying these stages transcriptional activation explained. review focuses activated multiple work together regulate gene expression. We illustrate currently understood principles mammalian they may be perturbed enhanceropathies using expression α‐globin cluster erythropoiesis, as model.

Язык: Английский

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Chromatin insulator mechanisms ensure accurate gene expression by controlling overall 3D genome organization

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 87, С. 102208 - 102208

Опубликована: Май 28, 2024

Язык: Английский

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Transcriptional machinery as an architect of genome structure

Current Opinion in Structural Biology, Год журнала: 2024, Номер 89, С. 102920 - 102920

Опубликована: Сен. 21, 2024

Язык: Английский

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Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 22, 2024

Abstract The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that is required for post-mitotic differentiation and function antigen-presenting dendritic cells (DCs), particularly antigen cross-presentation IL-12 secretion by type 1 conventional DCs (cDC1s) in vivo . organization was shaped DC-specifying transcription factor IRF8, which controlled looping chromosome compartmentalization, respectively. Notably, optimal expression IRF8 itself CTCF/cohesin-binding sites demarcating Irf8 gene. During DC activation, induction a subset genes with distal enhancers. Accordingly, deletion CTCF flanking Il12b gene reduced production cDC1s. Our data reveal an essential role cohesin-mediated regulation cell , its bi-directional crosstalk lineage-specifying factors.

Язык: Английский

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