The first embryonic landscape of G-quadruplexes related to myogenesis
Lijin Guo,
Weiling Huang,
Qi Wen,
Siyu Zhang,
Farhad Bordbar,
Zhengzhong Xiao,
Qinghua Nie
Affiliations
Lijin Guo
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Weiling Huang
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Qi Wen
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Siyu Zhang
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Farhad Bordbar
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Zhengzhong Xiao
Henry Fok School of Biology and Agriculture, Shaoguan University
Qinghua Nie
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University
Abstract Background DNA G-quadruplexes (G4s) represent a distinctive class of non-canonical DNA secondary structures. Despite their recognition as potential therapeutic targets in some cancers, the developmental role of G4 structures remains enigmatic. Mammalian embryonic myogenesis studies are hindered by limitations, prompting the use of chicken embryo-derived myoblasts as a model to explore G4 dynamics. This study aims to reveal the embryonic G4s landscape and elucidate the underlying mechanisms for candidate G4s that influence embryonic myogenesis. Results This investigation unveils a significant reduction in G4s abundance during myogenesis. G4s stabilizer pyridostatin impedes embryonic myogenesis, emphasizing the regulatory role of G4s in this process. G4 Cut&Tag sequencing and RNA-seq analyses identify potential G4s and DEGs influencing embryonic myogenesis. Integration of G4 and DEG candidates identifies 32 G4s located in promoter regions capable of modulating gene transcription. WGBS elucidates DNA methylation dynamics during embryonic myogenesis. Coordinating transcriptome data with DNA G4s and DNA methylation profiles constructs a G4-DMR-DEG network, revealing nine interaction pairs. Notably, the NFATC2 promoter region sequence is confirmed to form a G4 structure, reducing promoter mCpG content and upregulating NFATC2 transcriptional activity. Conclusions This comprehensive study unravels the first embryonic genomic G4s landscape, highlighting the regulatory role of NFATC2 G4 in orchestrating transcriptional activity through promoter DNA methylation during myogenesis.
