SMCHD1 terminates the first embryonic genome activation event in mouse two-cell embryos and contributes to a transcriptionally repressive state.
Am J Physiol Cell Physiol
; 317(4): C655-C664, 2019 10 01.
Article
en En
| MEDLINE
| ID: mdl-31365290
Embryonic genome activation (EGA) in mammals begins with transient expression of a large group of genes (EGA1). Importantly, entry into and exit from the 2C/EGA state is essential for viability. Dux family member genes play an integral role in EGA1 by activating other EGA marker genes such as Zscan4 family members. We previously reported that structural maintenance of chromosomes flexible hinge domain-containing protein 1 (Smchd1) is expressed at the mRNA and protein levels in mouse oocytes and early embryos and that elimination of Smchd1 expression inhibits inner cell mass formation, blastocyst formation and hatching, and term development. We extend these observations here by showing that siRNA knockdown of Smchd1 in zygotes results in overexpression of Dux and Zscan4 in two-cell embryos, with continued overexpression of Dux at least through the eight-cell stage as well as prolonged expression of Zscan4. These results are consistent with a role for SMCHD1 in promoting exit from the EGA1 state and establishing SMCHD1 as a maternal effect gene and the first chromatin regulatory factor identified with this role. Additionally, bioinformatics analysis reveals that SMCHD1 also contributes to the creation of a transcriptionally repressive state to allow correct gene regulation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oocitos
/
Blastocisto
/
Proteínas Cromosómicas no Histona
/
Genoma
/
Regulación del Desarrollo de la Expresión Génica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Asunto de la revista:
FISIOLOGIA
Año:
2019
Tipo del documento:
Article
Pais de publicación:
Estados Unidos