首页|Pivotal role for long noncoding RNAs in zygotic genome activation in mice

Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains unclear.The existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ZGA.Here,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor ZGA.Compared with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor ZGA.Distinct H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolⅡ pre-configuration.Furthermore,we identified the presence of PolⅡ-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo development.Our study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for under-standing the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

ZGAlncRNAMuERV-L

Kang Chen、Wenju Liu、Jiang Zhu、Xiaochen Kou、Yanhong Zhao、Hong Wang、Cizhong Jiang、Shaorong Gao、Lan Kang

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Institute for Regenerative Medicine,Shanghai East Hospital,Shanghai Key Laboratory of Signaling and Disease Research,School of Life Sciences and Technology,Tongji University,Shanghai 200120,China

Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100049,China

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education,Orthopaedic Department of Tongji Hospital,Shanghai Key Laboratory of Signaling and Disease Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China

Frontier Science Center for Stem Cell Research,Tongji University,Shanghai 200092,China

Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central Universities

2018YFA08001012022YFC27022002019YFA01100002021YFA1100300.2022YFA11031033217080131721003318714893237087031801243319728823227085822120230292

2024

10.1007/s11427-023-2502-5

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(5)