Abstract
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.
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Data availability
DNase-seq and RNA-seq datasets generated in this study were deposited in the Genome Sequence Archive (GSA) under accession CRA006639.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (31902161), the National Key Research and Development Program of China (2022YFD1302201, 2018YFA0107001), Strategic Priority Research Program of Chinese Academy of Sciences (XDA24020203), Key Research and Development Program of Hubei Province (2021BBA221), Major Project of Hubei Hongshan Laboratory (2021hszd003) and Foundation of Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, Guizhou University (QJHKY[2022]373). The authors thank Prof. Heide Schatten (University of Missouri-Columbia) for providing guidance and improving the language. The computations in this paper were run on the bioinformatics computing platform ofthe National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University.
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Zhu, W., Bu, G., Hu, R. et al. KLF4 facilitates chromatin accessibility remodeling in porcine early embryos. Sci. China Life Sci. 67, 96–112 (2024). https://doi.org/10.1007/s11427-022-2349-9
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DOI: https://doi.org/10.1007/s11427-022-2349-9