Coordinated alternation of DNA methylation and alternative splicing of PBRM1 affect bovine sperm structure and motility

Chunhong Yang; Yao Xiao; Xiuge Wang; Xiaochao Wei; Jinpeng Wang; Yaping Gao; Qiang Jiang; Zhihua Ju; Yaran Zhang; Wenhao Liu; Ning Huang; Yanqin Li; Yundong Gao; Lingling Wang; Jinming Huang

doi:10.1080/15592294.2023.2183339

Coordinated alternation of DNA methylation and alternative splicing of PBRM1 affect bovine sperm structure and motility

Epigenetics. 2023 Dec;18(1):2183339. doi: 10.1080/15592294.2023.2183339.

Authors

Chunhong Yang^{1

2}, Yao Xiao^{1

2}, Xiuge Wang^{1

2}, Xiaochao Wei^{1

2}, Jinpeng Wang^{1

2}, Yaping Gao^{1

2}, Qiang Jiang^{1

2}, Zhihua Ju^{1

2

3}, Yaran Zhang^{1

2}, Wenhao Liu^{1

2}, Ning Huang^{1

2}, Yanqin Li^{1

2}, Yundong Gao^{1

2}, Lingling Wang^{1

2}, Jinming Huang^{1

2

3}

Affiliations

¹ Key Laboratory of Livestock and Poultry Multi-omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, P. R. China.
² Shandong Key Laboratory of Animal Disease Control and Breeding, Jinan, P.R.China.
³ College of Life Sciences, Shandong Normal University, Jinan, P. R. China.

Abstract

DNA methylation and gene alternative splicing drive spermatogenesis. In screening DNA methylation markers and transcripts related to sperm motility, semen from three pairs of full-sibling Holstein bulls with high and low motility was subjected to reduced representation bisulphite sequencing. A total of 948 DMRs were found in 874 genes (gDMRs). Approximately 89% of gDMR-related genes harboured alternative splicing events, including SMAD2, KIF17, and PBRM1. One DMR in exon 29 of PBRM1 with the highest 5mC ratio was found, and hypermethylation in this region was related to bull sperm motility. Furthermore, alternative splicing events at exon 29 of PBRM1 were found in bull testis, including PBRM1-complete, PBRM1-SV1 (exon 28 deletion), and PBRM1-SV2 (exons 28-29 deletion). PBRM1-SV2 exhibited significantly higher expression in adult bull testes than in newborn bull testes. In addition, PBRM1 was localized to the redundant nuclear membrane of bull sperm, which might be related to sperm motility caused by sperm tail breakage. Therefore, the hypermethylation of exon 29 may be associated with the production of PBRM1-SV2 in spermatogenesis. These findings indicated that DNA methylation alteration at specific loci could regulate gene splicing and expression and synergistically alter sperm structure and motility.

Keywords: Alternative splicing; PBRM1; dairy cattle; epigenetic regulation; spermatogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing
Animals
Cattle
DNA Methylation*
Male
Semen*
Sperm Motility / genetics
Spermatozoa

Grants and funding

This work was supported by the National Key Research and Development Program of China (grant number 2021YFF1000703), National Natural Science Foundation of China (grant number 32002182), Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences (CXGC2022A05), Shandong Key Research and Development Program (2021LZGC011); and Shandong Agricultural Elite Variety Project (grant number 2019LZGC011).