Dynamic nucleosome organization after fertilization reveals regulatory factors for mouse zygotic genome activation

Year: 2022

Type: article

Abstract: Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored. Here, we investigated the dynamic changes in nucleosome occupancy and positioning in pronucleus-stage zygotes using ultra low-input MNase-seq. We observed distinct features of inheritance and reconstruction of nucleosome positioning in both paternal and maternal genomes. Genome-wide de novo nucleosome occupancy in the paternal genome was observed as early as 1 h after the injection of sperm into ooplasm. The nucleosome positioning pattern was continually rebuilt to form nucleosome-depleted regions (NDRs) at promoters and transcription factor (TF) binding sites with differential dynamics in paternal and maternal genomes. NDRs formed more quickly on the promoters of genes involved in zygotic genome activation (ZGA), and this formation is closely linked to histone acetylation, but not transcription elongation or DNA replication. Importantly, we found that NDR establishment on the binding motifs of specific TFs might be associated with their potential pioneer functions in ZGA. Further investigations suggested that the predicted factors MLX and RFX1 played important roles in regulating minor and major ZGA, respectively. Our data not only elucidate the nucleosome positioning dynamics in both male and female pronuclei following fertilization, but also provide an efficient method for identifying key transcription regulators during development.

Source: Cell Research

DOI: 10.1038/s41422-022-00652-8

Authors: Chenfei Wang, Chuan Chen, Xiaoyu Liu, Chong Li, Qiu Wu, Xiaolan Chen, Lingyue Yang, Xiaochen Kou, Yanhong Zhao, Hong Wang, Yawei Gao, Yong Zhang, Shaorong Gao

Institutions: Tongji University, Shanghai East Hospital, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang University, Shanghai First Maternity and Infant Hospital

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,790

Funders: Natural Science Foundation of Shanghai, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Science and Technology Commission of Shanghai Municipality, Tongji University, Shanghai Rising-Star Program, National Postdoctoral Program for Innovative Talents, Fundamental Research Funds for the Central Universities

OpenAlex ID: W4224107018