Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells
Abstract Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by geneti...
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Nature Portfolio
2023-06-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-39477-3 |
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author | Marko Dunjić Felix Jonas Gilad Yaakov Roye More Yoav Mayshar Yoach Rais Ayelet-Hashahar Orenbuch Saifeng Cheng Naama Barkai Yonatan Stelzer |
author_facet | Marko Dunjić Felix Jonas Gilad Yaakov Roye More Yoav Mayshar Yoach Rais Ayelet-Hashahar Orenbuch Saifeng Cheng Naama Barkai Yonatan Stelzer |
author_sort | Marko Dunjić |
collection | DOAJ |
description | Abstract Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by genetically encoded exchange sensors. While exchange of all measured variants scales with transcription, we describe variant-specific associations with transcription elongation and Polycomb binding. We found considerable exchange of H3.1 and H2B variants in heterochromatin and repeat elements, contrasting the occupancy and little exchange of H3.3 in these regions. This unexpected association between H3.3 occupancy and exchange of canonical variants is also evident in active promoters and enhancers, and further validated by reduced H3.1 dynamics following depletion of H3.3-specific chaperone, HIRA. Finally, analyzing transgenic mice harboring H3.1 or H3.3 sensors demonstrates the vast potential of this system for studying histone exchange and its impact on gene expression regulation in vivo. |
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institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-13T01:54:41Z |
publishDate | 2023-06-01 |
publisher | Nature Portfolio |
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series | Nature Communications |
spelling | doaj.art-a3c432554ed24441bcde9d8cfc86b4252023-07-02T11:20:03ZengNature PortfolioNature Communications2041-17232023-06-0114111910.1038/s41467-023-39477-3Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cellsMarko Dunjić0Felix Jonas1Gilad Yaakov2Roye More3Yoav Mayshar4Yoach Rais5Ayelet-Hashahar Orenbuch6Saifeng Cheng7Naama Barkai8Yonatan Stelzer9Department of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Genetics, Weizmann Institute of ScienceDepartment of Molecular Genetics, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Molecular Genetics, Weizmann Institute of ScienceDepartment of Molecular Cell Biology, Weizmann Institute of ScienceAbstract Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here, we define the genome-wide occupancy and exchange pattern of canonical and non-canonical histone variants in mouse embryonic stem cells by genetically encoded exchange sensors. While exchange of all measured variants scales with transcription, we describe variant-specific associations with transcription elongation and Polycomb binding. We found considerable exchange of H3.1 and H2B variants in heterochromatin and repeat elements, contrasting the occupancy and little exchange of H3.3 in these regions. This unexpected association between H3.3 occupancy and exchange of canonical variants is also evident in active promoters and enhancers, and further validated by reduced H3.1 dynamics following depletion of H3.3-specific chaperone, HIRA. Finally, analyzing transgenic mice harboring H3.1 or H3.3 sensors demonstrates the vast potential of this system for studying histone exchange and its impact on gene expression regulation in vivo.https://doi.org/10.1038/s41467-023-39477-3 |
spellingShingle | Marko Dunjić Felix Jonas Gilad Yaakov Roye More Yoav Mayshar Yoach Rais Ayelet-Hashahar Orenbuch Saifeng Cheng Naama Barkai Yonatan Stelzer Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells Nature Communications |
title | Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
title_full | Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
title_fullStr | Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
title_full_unstemmed | Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
title_short | Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
title_sort | histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells |
url | https://doi.org/10.1038/s41467-023-39477-3 |
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