High-throughput functional characterization of enhancers in totipotent-like cells

Abstract Zygotic genome activation (ZGA) marks the initial transcription event in embryogenesis, yet the cis -regulatory mechanism remains unclear. Here, utilizing massively parallel reporter assays, we functionally dissect enhancers across mouse genome in DUX-induced 2C-like cells (2CLCs). Integrated analysis with epigenomic and transcriptomic data from 2CLCs and 2-cell (2C) embryos, active enhancers in totipotent cells are depicted. Among them, a notable proportion of promoters exhibit enhancer activities, showing elevated active chromatin features and correlating with enhanced gene expression during ZGA. Furthermore, only half of the MT2_Mm exhibit enhancer activities in 2CLCs. In addition, 2CLC enhancers augment transcription in 2C embryos. Finally, deleting enhancer regions in both 2CLCs and 2C embryos highlighted their crucial role in facilitating transcription of ZGA genes. These findings advance our comprehension of the cis -regulatory mechanism governing ZGA process.

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Publication Details

Journal
Nature Communications
Published
2026-09-01
DOI
https://doi.org/10.1038/s41467-026-77311-8
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
0.00

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article

High-throughput functional characterization of enhancers in totipotent-like cells

Lingyue Yang, Xuzhao Zhai, Jiekai Chen, Yating Zhu et al.
Nature Communications
Genomics and Chromatin Dynamics
article

High-throughput functional characterization of enhancers in totipotent-like cells

Lingyue Yang, Xuzhao Zhai, Jiekai Chen, Yating Zhu, Dan Liang, Tianran Peng, Boyen Huang, Man Zhang, Yunxia Cao, Jiangping He, Tao Zhang, Hai Zhou, Ling Li, Tao Zhang
article en

Abstract

Abstract Zygotic genome activation (ZGA) marks the initial transcription event in embryogenesis, yet the cis -regulatory mechanism remains unclear. Here, utilizing massively parallel reporter assays, we functionally dissect enhancers across mouse genome in DUX-induced 2C-like cells (2CLCs). Integrated analysis with epigenomic and transcriptomic data from 2CLCs and 2-cell (2C) embryos, active enhancers in totipotent cells are depicted. Among them, a notable proportion of promoters exhibit enhancer activities, showing elevated active chromatin features and correlating with enhanced gene expression during ZGA. Furthermore, only half of the MT2_Mm exhibit enhancer activities in 2CLCs. In addition, 2CLC enhancers augment transcription in 2C embryos. Finally, deleting enhancer regions in both 2CLCs and 2C embryos highlighted their crucial role in facilitating transcription of ZGA genes. These findings advance our comprehension of the cis -regulatory mechanism governing ZGA process.

Nature Communications
Ministry of Education of the People's Republic of China (CN), Sun Yat-sen University (CN), Chinese University of Hong Kong (HK), Anhui Medical University (CN), Chinese Academy of Sciences (CN), Hong Kong University of Science and Technology (HK), Guangzhou Institutes of Biomedicine and Health (CN), Guangzhou Experimental Station (CN), Second Affiliated Hospital of Guangzhou Medical University (CN), First Affiliated Hospital of Anhui Medical University (CN), Guangzhou Medical University (CN)
National Natural Science Foundation of China, Anhui Medical University, Guangdong Provincial Pearl River Talents Program
Openalex Percentile: Top 99%
Genomics and Chromatin Dynamics
DOIOpen Access PDFOpenAlex
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