Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan, 430070, China.
Sci China Life Sci. 2024 Jan;67(1):96-112. doi: 10.1007/s11427-022-2349-9. Epub 2023 Sep 7.
Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos. Current studies have illustrated several pioneer factors as being important for agricultural animals, but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear. By employing low-input DNase-seq (liDNase-seq), we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development. Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos. Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos, whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts. Furthermore, KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos. In addition, we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation, whereas knockdown of KLF4 disrupted this process. Taken together, our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.
先驱因子驱动的染色质可及性重塑对于早期胚胎的发育至关重要。目前的研究已经表明了几种先驱因子对于农业动物的重要性，但哪些是先驱因子，以及它们如何重塑猪早期胚胎的染色质可及性尚不清楚。通过采用低输入 DNase-seq（liDNase-seq），我们对猪早期胚胎的染色质可及性图谱进行了分析，揭示了猪植入前发育过程中独特的染色质可及性重编程模式。我们的数据表明，KLF4 在重塑猪早期胚胎的染色质可及性方面发挥着关键作用。敲低 KLF4 导致早期胚胎的染色质可及性降低，而 KLF4 的过表达则促进了猪囊胚的染色质开放性。此外，KLF4 的缺失导致了猪胚胎的线粒体功能障碍和发育失败。此外，我们发现 KLF4 在囊胚中的过表达促进了脂滴的积累，而 KLF4 的敲低则破坏了这个过程。总之，我们的研究揭示了染色质可及性的动态变化，并确定了 KLF4 作为猪植入前胚胎发育过程中染色质可及性和细胞代谢的关键调节因子。
