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

• Published in: Cell reports (Cambridge) 2024-06, Vol.43 (6), p.114372, Article 114372
• Main Authors: Zhou, Kai, Wang, Tingting, Zhang, Jingjing, Zhang, Jingcheng, Liu, Xingchen, Guan, Jiaqi, Su, Peng, Wu, Linhui, Yang, Xin, Hu, Ruifeng, Sun, Qiaoran, Fan, Zhengang, Yang, Shichun, Chu, Xiaoyu, Song, Wenting, Shang, Yan, Zhou, Songxian, Hao, Xingkun, Zhang, Xia, Sun, Qiang, Liu, Xin, Miao, Yi-Liang
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Blastocyst - metabolism; Cloning, Organism - methods; CP: Molecular biology; CP: Stem cell research; Embryo, Mammalian - metabolism; Embryonic Development - genetics; Gene Expression Regulation, Developmental; Genome; Histones - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Nuclear Transfer Techniques; Swine; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114372

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. [Display omitted] •LEUTX is transiently expressed during EGA in porcine and primate fertilized embryos•LEUTX restores EGA failure in porcine SCNT embryos and improves SCNT efficiency•LEUTX opens chromatin and establishes histone acetylation at its binding sites•LEUTX recruits p300 and KAT2A through its intermediate region Zhou et al. revealed the transient expression of PRD-like transcription factors during embryonic genome activation (EGA) in porcine and primate early embryos. They identified LEUTX as a key PRD-like activator of porcine EGA, and its overexpression promoted somatic cell reprogramming by establishing histone acetylation and enhancing chromatin accessibility.