Yang, FanHuang, XinZang, RugeChen, JiayuFidalgo Pérez, Miguel ÁngelSánchez Priego, CarlosYang, JihongCaichen, AlexanderMa, FanglinMacfarlan, ToddHuang, HuayanGao, ShaorongZhou, HongweiWang, Jianlong2025-01-162025-01-162020-02Fan 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.2020.01.004https://hdl.handle.net/10347/38618Mouse 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 potencyeng© 2020 Elsevier IncEndogenous retrovirusMERVLmiR-344Zmym2Lsd1DuxGata22C-like cellsTotipotency32 Ciencias médicasjournal article10.1016/j.stem.2020.01.0041875-9777open access