Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 29, 2022
- Source ID
- 10.1038/s41467-022-29730-6
Entities
People
- Andrew Volk
- Brian T Do
- Carmen Chiem
- David B Sykes
- David E Frankhouser
- Fei Ji
- Jernej Murn
- Konrad Hochedlinger
- M. Andres Blanco
- Maria Ninova
- Matthew G Vander Heiden
- Meijuan Chen
- Mihyun Jang
- Reuben Franklin
- Rui Lu
- Ruslan I Sadreyev
- Russell Rockne
- Shiyang He
- Sihem Cheloufi
- Xinyue Zhou
- Yiming Guo
Organizations
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of General Medical Sciences
- United States Department of Defense