Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region.
Brief Bioinform
; 22(4)2021 07 20.
Article
em En
| MEDLINE
| ID: mdl-33316032
ABSTRACT
Developmental pluripotency-associated 2 (Dppa2) and developmental pluripotency-associated 4 (Dppa4) as positive drivers were helpful for transcriptional regulation of zygotic genome activation (ZGA). Here, we systematically assessed the cooperative interplay of Dppa2 and Dppa4 in regulating cell pluripotency and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells (ESCs). Compared with other pluripotency transcription factors, Dppa2/4 can regulate majorities of signaling pathways by binding on CG-rich region of proximal promoter (0-500 bp), of which 85% and 77% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found alkaline phosphatase, placental-like 2 (Alppl2) was completely silenced when Dppa2 and 4 single- or double-knockout in ESC, which is consistent with Dux. Moreover, Alppl2 was significantly activated in mouse 2-cell embryos and 4-8 cells stage of human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a ZGA candidate driver to facilitate pre-embryonic development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Zigoto
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Proteínas Nucleares
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Transdução de Sinais
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Genoma Humano
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Ilhas de CpG
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article