Sangam: A Confluence of Knowledge Streams

Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity

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dc.contributor Massachusetts Institute of Technology. Department of Biology
dc.creator Franklin, Reuben
dc.creator Guo, Yiming
dc.creator He, Shiyang
dc.creator Chen, Meijuan
dc.creator Ji, Fei
dc.creator Zhou, Xinyue
dc.creator Frankhouser, David
dc.creator Do, Brian T
dc.creator Chiem, Carmen
dc.creator Jang, Mihyun
dc.creator Blanco, M Andres
dc.creator Vander Heiden, Matthew G
dc.creator Rockne, Russell C
dc.creator Ninova, Maria
dc.creator Sykes, David B
dc.creator Hochedlinger, Konrad
dc.creator Lu, Rui
dc.creator Sadreyev, Ruslan I
dc.creator Murn, Jernej
dc.creator Volk, Andrew
dc.creator Cheloufi, Sihem
dc.date 2023-01-06T15:01:57Z
dc.date 2023-01-06T15:01:57Z
dc.date 2022
dc.date 2023-01-06T14:48:13Z
dc.date.accessioned 2023-03-01T18:11:38Z
dc.date.available 2023-03-01T18:11:38Z
dc.identifier https://hdl.handle.net/1721.1/146999
dc.identifier 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).
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/279102
dc.description <jats:title>Abstract</jats:title><jats:p>Cell 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.</jats:p>
dc.format application/pdf
dc.language en
dc.publisher Springer Science and Business Media LLC
dc.relation 10.1038/S41467-022-29730-6
dc.relation Nature Communications
dc.rights Creative Commons Attribution 4.0 International license
dc.rights https://creativecommons.org/licenses/by/4.0/
dc.source Nature
dc.title Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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