Nucleosome dynamics render heterochromatin accessible in living human cells

Abstract The eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin,...

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Main Authors: Hemant K. Prajapati, Zhuwei Xu, Peter R. Eriksson, David J. Clark
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59994-7
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author Hemant K. Prajapati
Zhuwei Xu
Peter R. Eriksson
David J. Clark
author_facet Hemant K. Prajapati
Zhuwei Xu
Peter R. Eriksson
David J. Clark
author_sort Hemant K. Prajapati
collection DOAJ
description Abstract The eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin, which is condensed and transcriptionally repressed. It is widely accepted that chromatin architecture modulates DNA accessibility, restricting the access of sequence-specific, gene-regulatory, transcription factors to the genome. However, the evidence for this model derives primarily from experiments with isolated nuclei, in which chromatin remodeling has ceased, resulting in a static chromatin structure. Here, using a DNA methyltransferase to measure accessibility in vivo, we show that both euchromatin and heterochromatin are fully accessible in living human cells, whereas centromeric α-satellite chromatin is partly inaccessible. We conclude that all nucleosomes in euchromatin and heterochromatin are highly dynamic in living cells, except for nucleosomes in centromeric chromatin.
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spelling doaj-art-a6548e0e7b9a469891b60bdcb5a6cd362025-08-20T02:25:17ZengNature PortfolioNature Communications2041-17232025-05-0116111110.1038/s41467-025-59994-7Nucleosome dynamics render heterochromatin accessible in living human cellsHemant K. Prajapati0Zhuwei Xu1Peter R. Eriksson2David J. Clark3Division of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of HealthDivision of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of HealthDivision of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of HealthDivision of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of HealthAbstract The eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin, which is condensed and transcriptionally repressed. It is widely accepted that chromatin architecture modulates DNA accessibility, restricting the access of sequence-specific, gene-regulatory, transcription factors to the genome. However, the evidence for this model derives primarily from experiments with isolated nuclei, in which chromatin remodeling has ceased, resulting in a static chromatin structure. Here, using a DNA methyltransferase to measure accessibility in vivo, we show that both euchromatin and heterochromatin are fully accessible in living human cells, whereas centromeric α-satellite chromatin is partly inaccessible. We conclude that all nucleosomes in euchromatin and heterochromatin are highly dynamic in living cells, except for nucleosomes in centromeric chromatin.https://doi.org/10.1038/s41467-025-59994-7
spellingShingle Hemant K. Prajapati
Zhuwei Xu
Peter R. Eriksson
David J. Clark
Nucleosome dynamics render heterochromatin accessible in living human cells
Nature Communications
title Nucleosome dynamics render heterochromatin accessible in living human cells
title_full Nucleosome dynamics render heterochromatin accessible in living human cells
title_fullStr Nucleosome dynamics render heterochromatin accessible in living human cells
title_full_unstemmed Nucleosome dynamics render heterochromatin accessible in living human cells
title_short Nucleosome dynamics render heterochromatin accessible in living human cells
title_sort nucleosome dynamics render heterochromatin accessible in living human cells
url https://doi.org/10.1038/s41467-025-59994-7
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AT peterreriksson nucleosomedynamicsrenderheterochromatinaccessibleinlivinghumancells
AT davidjclark nucleosomedynamicsrenderheterochromatinaccessibleinlivinghumancells