Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region

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...

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Bibliographic Details
Published in:Briefings in bioinformatics 2021-07, Vol.22 (4)
Main Authors: Li, Hanshuang, Long, Chunshen, Xiang, Jinzhu, Liang, Pengfei, Li, Xueling, Zuo, Yongchun
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Binding
Embryo cells
Embryogenesis
Embryonic growth stage
Embryos
Gene regulation
Genomes
MAP kinase
Pluripotency
Signal transduction
Signaling
Stem cell transplantation
Stem cells
Transcription factors
Zygotes
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Summary: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.
ISSN:1467-5463
1477-4054
DOI:10.1093/bib/bbaa342