Structure of native chromatin fibres revealed by Cryo-ET in situ

Abstract The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interpha...

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Main Authors: Zhen Hou, Frank Nightingale, Yanan Zhu, Craig MacGregor-Chatwin, Peijun Zhang
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-42072-1
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author Zhen Hou
Frank Nightingale
Yanan Zhu
Craig MacGregor-Chatwin
Peijun Zhang
author_facet Zhen Hou
Frank Nightingale
Yanan Zhu
Craig MacGregor-Chatwin
Peijun Zhang
author_sort Zhen Hou
collection DOAJ
description Abstract The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.
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spelling doaj.art-7bf6990435a04087b22089f9ed313e332023-11-20T10:17:17ZengNature PortfolioNature Communications2041-17232023-10-011411710.1038/s41467-023-42072-1Structure of native chromatin fibres revealed by Cryo-ET in situZhen Hou0Frank Nightingale1Yanan Zhu2Craig MacGregor-Chatwin3Peijun Zhang4Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of OxfordDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of OxfordDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of OxfordDiamond Light Source, Harwell Science and Innovation CampusDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of OxfordAbstract The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.https://doi.org/10.1038/s41467-023-42072-1
spellingShingle Zhen Hou
Frank Nightingale
Yanan Zhu
Craig MacGregor-Chatwin
Peijun Zhang
Structure of native chromatin fibres revealed by Cryo-ET in situ
Nature Communications
title Structure of native chromatin fibres revealed by Cryo-ET in situ
title_full Structure of native chromatin fibres revealed by Cryo-ET in situ
title_fullStr Structure of native chromatin fibres revealed by Cryo-ET in situ
title_full_unstemmed Structure of native chromatin fibres revealed by Cryo-ET in situ
title_short Structure of native chromatin fibres revealed by Cryo-ET in situ
title_sort structure of native chromatin fibres revealed by cryo et in situ
url https://doi.org/10.1038/s41467-023-42072-1
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AT yananzhu structureofnativechromatinfibresrevealedbycryoetinsitu
AT craigmacgregorchatwin structureofnativechromatinfibresrevealedbycryoetinsitu
AT peijunzhang structureofnativechromatinfibresrevealedbycryoetinsitu