Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity.
Nat Commun
; 13(1): 2350, 2022 04 29.
Article
em En
| MEDLINE
| ID: mdl-35487911
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Chaperonas de Histonas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article