RT Journal Article
T1 DUX-miR-344-ZMYM2-Mediated Activation of MERVL LTRs Induces a Totipotent 2C-like State
A1 Yang, Fan
A1 Huang, Xin
A1 Zang, Ruge
A1 Chen, Jiayu
A1 Fidalgo Pérez, Miguel Ángel
A1 Sánchez Priego, Carlos
A1 Yang, Jihong
A1 Caichen, Alexander
A1 Ma, Fanglin
A1 Macfarlan, Todd
A1 Huang, Huayan
A1 Gao, Shaorong
A1 Zhou, Hongwei
A1 Wang, Jianlong
K1 Endogenous retrovirus
K1 MERVL
K1 miR-344
K1 Zmym2
K1 Lsd1
K1 Dux
K1 Gata2
K1 2C-like cells
K1 Totipotency
AB Mouse embryonic stem cells (ESCs) sporadically express preimplantation two-cell-stage (2C) transcripts, including MERVL endogenous retrovirus and Zscan4 cluster genes. Such 2C-like cells (2CLCs) can contribute to both embryonic and extraembryonic tissues when reintroduced into early embryos, although the molecular mechanism underlying such an expanded 2CLC potency remains elusive. We examine global nucleosome occupancy and gene expression in 2CLCs and identified miR-344 as the noncoding molecule that positively controls 2CLC potency. We find that activation of endogenous MERVL or miR-344-2 alone is sufficient to induce 2CLCs with activation of 2C genes and an expanded potency. Mechanistically, miR-344 is activated by DUX and post-transcriptionally represses ZMYM2 and its partner LSD1, and ZMYM2 recruits LSD1/HDAC corepressor complex to MERVL LTR for transcriptional repression. Consistently, zygotic depletion of Zmym2 compromises the totipotency-to-pluripotency transition during early development. Our studies establish the previously unappreciated DUX-miR-344-Zmym2/Lsd1 axis that controls MERVL for expanded stem cell potency
PB Elsevier
YR 2020
FD 2020-02
LK https://hdl.handle.net/10347/38618
UL https://hdl.handle.net/10347/38618
LA eng
NO Fan Yang, Xin Huang, Ruge Zang, Jiayu Chen, Miguel Fidalgo, Carlos Sanchez-Priego, Jihong Yang, Alexander Caichen, Fanglin Ma, Todd Macfarlan, Huayan Wang, Shaorong Gao, Hongwei Zhou, Jianlong Wang, DUX-miR-344-ZMYM2-Mediated Activation of MERVL LTRs Induces a Totipotent 2C-like State, Cell Stem Cell, Volume 26, Issue 2, 2020, Pages 234-250.e7, ISSN 1934-5909, https://doi.org/10.1016/j.stem.2020.01.004
DS Minerva
RD 23 abr 2026