Transcription factor AP-2 gamma affects porcine early embryo development by regulating epigenetic modification

Daoyu Zhang; Di Wu; Sheng Zhang; Meng Zhang; Yongfeng Zhou; Xinglan An; Qi Li; Ziyi Li

doi:10.1016/j.rbmo.2023.103772

Transcription factor AP-2 gamma affects porcine early embryo development by regulating epigenetic modification

Reprod Biomed Online. 2023 Dec 17:103772. doi: 10.1016/j.rbmo.2023.103772. Online ahead of print.

Authors

Daoyu Zhang¹, Di Wu², Sheng Zhang¹, Meng Zhang³, Yongfeng Zhou¹, Xinglan An¹, Qi Li¹, Ziyi Li⁴

Affiliations

¹ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun 130021, China.
² First Hospital, Jilin University, Changchun 130021, China.
³ The Jackson Laboratory for Genome Technology, 10 Discovery Drive Farmington, Connecticut, 06932, USA.
⁴ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun 130021, China.. Electronic address: ziyi@jlu.edu.cn.

PMID: 38749801
DOI: 10.1016/j.rbmo.2023.103772

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.

Keywords: DNA methylation; SETD2; TFAP2C; histone modification; porcine embryo development.