Species-specific roles of SP1 in bovine and human embryonic genome activation and early embryonic development

H Hao Jin (State Key Laboratory of Medical Proteomics, National Chromatographic Research & Analysis Center, Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences) L Lieying Xiao (Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University) X Xiaolin He (Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University) B Bingjie Hu (Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University) Y Yan Shi B Bo Xu X Xiaomei Tong (Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Shaw Hospital, Zhejiang University, School of Medicine) S Shaohua Wang (State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry) P Panpan Zhao (State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry) L Lei Luo (State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023, P. R. China) K Kun Zhang

Abstract

Embryonic genome activation (EGA) marks the onset of the embryonic program and enables the transition toward the first lineage specification. However, the molecular features of EGA and the transcription factors (TFs) orchestrating this process remain unclear. Here, by performing single-cell RNA-seq on bovine embryos, we reveal that major EGA is asynchronously initiated among blastomeres at the 8-cell stage. Integrative analyses reveal distinct protein accumulation compared with transcriptional and translational activation during bovine EGA. Furthermore, we investigate the role of SP1, a TF activated at the minor EGA stage, with motifs enriched in accessible chromatin during the major EGA stage in bovine and human embryos. SP1 deficiency leads to morula arrest in bovine and impairs EGA in human embryos. Multiomics analysis demonstrates that SP1 promotes early lineage gene expression by modulating nearby chromatin states in bovine and directly targets key EGA genes in human embryos. Together, our study delineates the dynamics of bovine EGA and uncovers the conserved and species-specific roles of SP1 in regulating EGA and early development in mammals.

Article Details

Volume / Issue Vol. 123, Issue 12
Published March 24, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (11)

H

Hao Jin

State Key Laboratory of Medical Proteomics, National Chromatographic Research & Analysis Center, Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences

L

Lieying Xiao

Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University

X

Xiaolin He

Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University

B

Bingjie Hu

Laboratory of Mammalian Molecular Embryology, Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University

Y

Yan Shi

B

Bo Xu

X

Xiaomei Tong

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Shaw Hospital, Zhejiang University, School of Medicine

S

Shaohua Wang

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry

P

Panpan Zhao

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry

L

Lei Luo

State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023, P. R. China

K

Kun Zhang