Document Type

Article

Publication Date

10-1-2024

Keywords

JGM, Animals, Female, DNA Methylation, Embryonic Development, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Swine, Transcription Factor AP-2

JAX Source

Reprod Biomed Online. 2024;49(4):103772.

ISSN

1472-6491

PMID

38749801

DOI

https://doi.org/10.1016/j.rbmo.2023.103772

Grant

This work was supported by National Natural Science Foundation (number: 31972874), Jilin Province Health Science and Technology Capacity Improvement Project (number: 2021JC006), Jilin Natural Science Foundation (number: YDZJ202201ZYTS445), Jilin Medical and Health Talents Project (number: JLSWSRCZX2021-112) in China.

Abstract

RESEARCH QUESTION: What is the role and mechanism of action of transcription factor AP-2 gamma (TFAP2C) in porcine early embryo development?

DESIGN: TFAP2C siRNA were injected into porcine oocytes, which subsequently underwent IVF. Different stages of embryos were collected for RNA sequencing, quantitative polymerase chain reaction, immunofluorescence staining to explore the affects in gene expression and epigenetic modification. Porcine fetal fibroblasts were transfected with siRNA, and cells were collected for chromatin immunoprecipitation and dual luciferase reporter assays.

RESULTS: The deficiency of TFAP2C led to disorders in early embryonic development; 1208 genes were downregulated and 792 genes were upregulated in TFAP2C knockdown (TFAP2C-KD) embryos. The expression of epigenetic modification enzymes KDM5B, SETD2 were significantly elevated in the TFAP2C-KD group (P < 0.001). Meanwhile, the modification levels of H3K4me3 and H3K4me2 were significantly decreased (P = 0.0021, P = 0.0029), and H3K36me3 and DNA methylation were significantly increased in TFAP2C-KD group (P = 0.0045, P = 0.0025). DNMT1 was mainly expressed in nuclei in the TFAP2C-KD group (P = 0.0103). In addition, TFAP2C could bind to the promoter region of SETD2, and the mutation of the TFAP2C binding site resulted in increased activity of SETD2 promoter (P < 0.001).

CONCLUSIONS: The knockdown of TFAP2C affects early embryonic development by regulating histone modification and DNA methylation.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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