PMID- 35721479
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - Maternal Factor Dppa3 Activates 2C-Like Genes and Depresses DNA Methylation in 
      Mouse Embryonic Stem Cells.
PG  - 882671
LID - 10.3389/fcell.2022.882671 [doi]
LID - 882671
AB  - Mouse embryonic stem cells (ESCs) contain a rare cell population of "two-cell 
      embryonic like" cells (2CLCs) that display similar features to those found in the 
      two-cell (2C) embryo and thus represent an in vitro model for studying the 
      progress of zygotic genome activation (ZGA). However, the positive regulator 
      determinants of the 2CLCs' conversion and ZGA have not been completely 
      elucidated. Here, we identify a new regulator promoting 2CLCs and ZGA 
      transcripts. Through a combination of overexpression (OE), knockdown (KD), 
      together with transcriptional analysis and methylome analysis, we find that Dppa3 
      regulates the 2CLC-associated transcripts, DNA methylation, and 2CLC population 
      in ESCs. The differentially methylated regions (DMRs) analysis identified 6,920 
      (98.2%) hypomethylated, whilst only 129 (1.8%) hypermethylated, regions in Dppa3 
      OE ESCs, suggesting that Dppa3 facilitates 2CLCs reprogramming. The conversion to 
      2CLCs by overexpression of Dppa3 is also associated with DNA damage response. 
      Dppa3 knockdown manifest impairs transition into the 2C-like state. Global DNA 
      methylome and chromatin state analysis of Dppa3 OE ESCs reveal that Dppa3 
      facilitates the chromatin configuration to 2CLCs reversion. Our finding for the 
      first time elucidates a novel role of Dppa3 in mediating the 2CLC conversion, and 
      suggests that Dppa3 is a new regulator for ZGA progress.
CI  - Copyright (c) 2022 Zhang, Wen, Liu, Fu, Yu, Chen, Han, Li and Liu.
FAU - Zhang, Chuanyu
AU  - Zhang C
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Wen, Hang
AU  - Wen H
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Liu, Siying
AU  - Liu S
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Fu, Enze
AU  - Fu E
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Yu, Lu
AU  - Yu L
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Chen, Shang
AU  - Chen S
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Han, Qingsheng
AU  - Han Q
AD  - School of Medicine, Nankai University, Tianjin, China.
FAU - Li, Zongjin
AU  - Li Z
AD  - School of Medicine, Nankai University, Tianjin, China.
AD  - Key Laboratory of Bioactive Materials, Ministry of Education, College of Life 
      Sciences Nankai University, Tianjin, China.
FAU - Liu, Na
AU  - Liu N
AD  - School of Medicine, Nankai University, Tianjin, China.
AD  - Key Laboratory of Bioactive Materials, Ministry of Education, College of Life 
      Sciences Nankai University, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20220603
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC9203971
OTO - NOTNLM
OT  - 2CLCs
OT  - DNA methylation
OT  - Dppa3
OT  - Embryonic stem cells
OT  - Zscan4
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/21 06:00
MHDA- 2022/06/21 06:01
PMCR- 2022/01/01
CRDT- 2022/06/20 03:55
PHST- 2022/02/24 00:00 [received]
PHST- 2022/04/25 00:00 [accepted]
PHST- 2022/06/20 03:55 [entrez]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2022/06/21 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 882671 [pii]
AID - 10.3389/fcell.2022.882671 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 Jun 3;10:882671. doi: 10.3389/fcell.2022.882671. 
      eCollection 2022.