Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells

Marko Dunjić, Felix Jonas, Gilad Yaakov, Roye More, Yoav Mayshar, Yoach Rais, Ayelet-Hashahar Orenbuch, Saifeng Cheng, Naama Barkai and Yonatan Stelzer ()
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Marko Dunjić: Weizmann Institute of Science
Felix Jonas: Weizmann Institute of Science
Gilad Yaakov: Weizmann Institute of Science
Roye More: Weizmann Institute of Science
Yoav Mayshar: Weizmann Institute of Science
Yoach Rais: Weizmann Institute of Science
Ayelet-Hashahar Orenbuch: Weizmann Institute of Science
Saifeng Cheng: Weizmann Institute of Science
Naama Barkai: Weizmann Institute of Science
Yonatan Stelzer: Weizmann Institute of Science

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39477-3

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