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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Main Authors: Marko Dunjić, Felix Jonas, Gilad Yaakov, Roye More, Yoav Mayshar, Yoach Rais, Ayelet-Hashahar Orenbuch, Saifeng Cheng, Naama Barkai, Yonatan Stelzer
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
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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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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