Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity
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s41467-022-29730-6.pdf
Description
Published version
Size
3.37 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Franklin, Reuben
Guo, Yiming
He, Shiyang
Chen, Meijuan
Ji, Fei
Zhou, Xinyue
Frankhouser, David
Do, Brian T
Chiem, Carmen
Jang, Mihyun
Date Issued
2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Franklin, Reuben, Guo, Yiming, He, Shiyang, Chen, Meijuan, Ji, Fei et al. 2022. "Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity." Nature Communications, 13 (1).
Version
Final published version
Abstract
AbstractCell fate commitment is driven by dynamic changes in chromatin architecture and activity of lineage-specific transcription factors (TFs). The chromatin assembly factor-1 (CAF-1) is a histone chaperone that regulates chromatin architecture by facilitating nucleosome assembly during DNA replication. Accumulating evidence supports a substantial role of CAF-1 in cell fate maintenance, but the mechanisms by which CAF-1 restricts lineage choice remain poorly understood. Here, we investigate how CAF-1 influences chromatin dynamics and TF activity during lineage differentiation. We show that CAF-1 suppression triggers rapid differentiation of myeloid stem and progenitor cells into a mixed lineage state. We find that CAF-1 sustains lineage fidelity by controlling chromatin accessibility at specific loci, and limiting the binding of ELF1 TF at newly-accessible diverging regulatory elements. Together, our findings decipher key traits of chromatin accessibility that sustain lineage integrity and point to a powerful strategy for dissecting transcriptional circuits central to cell fate commitment.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-022-29730-6
