Cell Reports (Jun 2024)

LEUTX regulates porcine embryonic genome activation in somatic cell nuclear transfer embryos

  • Kai Zhou,
  • Tingting Wang,
  • Jingjing Zhang,
  • Jingcheng Zhang,
  • Xingchen Liu,
  • Jiaqi Guan,
  • Peng Su,
  • Linhui Wu,
  • Xin Yang,
  • Ruifeng Hu,
  • Qiaoran Sun,
  • Zhengang Fan,
  • Shichun Yang,
  • Xiaoyu Chu,
  • Wenting Song,
  • Yan Shang,
  • Songxian Zhou,
  • Xingkun Hao,
  • Xia Zhang,
  • Qiang Sun,
  • Xin Liu,
  • Yi-Liang Miao

Journal volume & issue
Vol. 43, no. 6
p. 114372

Abstract

Read online

Summary: Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

Keywords