CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos.
Int J Biol Macromol
; 195: 547-557, 2022 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-34906611
ABSTRACT
Chromatin assembly factor-1, subunit b (CHAF1b), the p60 subunit of the chromatin-assembly factor-1 (CAF-1) complex, is an evolutionarily conserved protein that has been implicated in various biological processes. Although a variety of functions have been attributed to CHAF1b, its function in preimplantation embryos remains obscure. In this study, we showed that CHAF1b knockdown did not affect the blastocyst rate, but resulted in a low blastocyst hatching rate, outgrowth failure in vitro, and embryonic lethality after implantation in vivo. Notably, CHAF1b depletion increased apoptosis and caused down-regulated expression of key regulators of cell fate specification, including Oct4, Cdx2, Sox2, and Nanog. Further analysis revealed that CHAF1b mediated the replacement of H3.3 with H3.1/3.2, which was associated with decreased repressive histone marks (H3K9me2/3 and H3K27me2/3) and increased active histone marks (H3K4me2/3). Moreover, RNA-sequencing analysis revealed that CHAF1b depletion resulted in the differential expression of 1508 genes, including epigenetic modifications genes, multiple lineage-specific genes, and several genes encoding apoptosis proteins. In addition, assay for transposase-accessible chromatin-sequencing analysis demonstrated that silencing CHAF1b altered the chromatin accessibility of lineage-specific genes and epigenetic modifications genes. Taken together, these data imply that CHAF1b plays significant roles in preimplantation embryos, probably by regulating epigenetic modifications and lineage specification.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Blastocisto
/
Regulación del Desarrollo de la Expresión Génica
/
Desarrollo Embrionario
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Factor 1 de Ensamblaje de la Cromatina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2022
Tipo del documento:
Article