Regulation of Chromatin Accessibility by the Histone Chaperone CAF-1 Sustains Lineage Fidelity

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Apr 29

PMID 35487911

Authors

Reuben Franklin

Yiming Guo

Shiyang He

Meijuan Chen

Fei Ji

Xinyue Zhou

David Frankhouser

Brian T Do

Carmen Chiem

Mihyun Jang

M Andres Blanco

Matthew G Vander Heiden

Russell C Rockne

Maria Ninova

David B Sykes

Konrad Hochedlinger

Rui Lu

Ruslan I Sadreyev

Jernej Murn

Andrew Volk

Sihem Cheloufi

Affiliations

Soon will be listed here.

Abstract

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.

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