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  3. CANTAC-seq analysis reveals E2f1 and Otx1 coordinate zygotic genome activation in Xenopus tropicalis

CANTAC-seq analysis reveals E2f1 and Otx1 coordinate zygotic genome activation in Xenopus tropicalis

  • Nat Commun. 2025 Nov 18;16(1):10101. doi: 10.1038/s41467-025-65146-8.
Huanhuan Cui # 1 2 3,  Weizheng Liang # 4 5 6,  Zhaoying Shi # 7 8,  Luming Zhang # 4 5,  Guipeng Li 4 5 9,  Rui Chen 4 5,  Chi Tian 4 5,  Diwen Gan 4 5,  Xinyao Shi 4 5,  Zhiyuan Sun 4 5,  Qionghua Zhu 4 5 9,  Liang Fang 4 5 9,  Hongda Huang 7 10,  Yuhui Hu 4 11,  Yonglong Chen 7,  Wei Chen 12 13 14
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 2 Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 3 Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 4 Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
  • 5 Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
  • 6 Hebei Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
  • 7 Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
  • 8 Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, Department of Physiology, School of Basic Medical Sciences, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.
  • 9 Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, China.
  • 10 Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
  • 11 Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
  • 12 Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 13 Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • 14 Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, China. [email protected].
  • # Contributed equally.
PMID: 41253814 DOI: 10.1038/s41467-025-65146-8
Abstract

Zygotic genome activation is tightly associated with the modulation of chromatin accessibility via maternal transcription factors. Understanding how chromatin accessibility is established and identifying key maternal regulators are crucial to comprehending this process. Here, by developing CANTAC-seq, we generate a genome-wide map of accessible chromatin of early Xenopus tropicalis embryos and find that the open chromatin landscape is progressively established at cis-regulatory elements during zygotic genome activation. Based on the motif analysis and perturbation experiments, we demonstrate that E2f1 maintains a repressive chromatin environment and inhibits zygotic gene transcription before the mid-blastula transition. Moreover, we identify that Otx1, another maternal transcriptional activator, coordinates with E2f1 in regulating chromatin accessibility and zygotic genome activation. Together, E2f1 and Otx1 determine the timely expression of a subset of genes required for zygotic gene transcription and germ layer differentiation.

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