AUTHOR=Zhang Chuanyu , Wen Hang , Liu Siying , Fu Enze , Yu Lu , Chen Shang , Han Qingsheng , Li Zongjin , Liu Na 

TITLE=Maternal Factor Dppa3 Activates 2C-Like Genes and Depresses DNA Methylation in Mouse Embryonic Stem Cells

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.882671

DOI=10.3389/fcell.2022.882671

ISSN=2296-634X

ABSTRACT=<p>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 <italic>in vitro</italic> 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 <italic>Dppa3</italic> OE ESCs, suggesting that Dppa3 facilitates 2CLCs reprogramming. The conversion to 2CLCs by overexpression of <italic>Dppa3</italic> is also associated with DNA damage response. <italic>Dppa3</italic> knockdown manifest impairs transition into the 2C-like state. Global DNA methylome and chromatin state analysis of <italic>Dppa3</italic> OE ESCs reveal that <italic>Dppa3</italic> 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.</p>