Dynamic DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine Reprogramming During Early Human Development  

作　　者：Xiao Han Jia Guo Mengke Wang Nan Zhang Jie Ren Ying Yang Xu Chi Yusheng Chen Huan Yao Yong-Liang Zhao Yun-Gui Yang Yingpu Sun Jiawei Xu 

机构地区：[1]Center for Reproductive Medicine,Henan Key Laboratory of Reproduction and Genetics,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China [2]Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Sino-Danish College,University of Chinese Academy of Sciences,Beijing 100049,China [5]Institute of Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Genomics, Proteomics & Bioinformatics》2023年第4期805-822,共18页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Key R&D Program of China(Grant Nos.2019YFA0110900,2019YFA0802202,2019YFA0802200 and 2020YFA0803401);the National Natural Science Foundation of China(Grant Nos.31870817 and 32170819);the Scientific and Technological Innovation Talent Project of Universities of Henan Province,China(Grant No.20HASTIT045);the Shanghai Municipal Science and Technology Major Project,China(Grant No.2017SHZDZX01);the China Postdoctoral Science Foundation(Grant No.2021M692927).

摘　　要：After implantation,complex and highly specialized molecular events render functionally distinct organ formation,whereas how the epigenome shapes organ-specific development remains to be fully elucidated.Here,nano-hmC-Seal,RNA bisulfite sequencing(RNA-BisSeq),and RNA sequencing(RNA-Seq)were performed,and the first multilayer landscapes of DNA 5-hydroxymethylcytosine(5hmC)and RNA 5-methylcytosine(m^(5)C)epigenomes were obtained in the heart,kidney,liver,and lung of the human foetuses at 13-28 weeks with 123 samples in total.We identified 70,091 and 503 organ-and stage-specific differentially hydroxymethylated regions(DhMRs)and m^(5)C-modified mRNAs,respectively.The key transcription factors(TFs),T-box transcription factor 20(TBX20),paired box 8(PAX8),krueppel-like factor 1(KLF1),transcription factor 21(TCF21),and CCAAT enhancer binding protein beta(CEBPB),specifically contribute to the formation of distinct organs at different stages.Additionally,5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes.Our integrated studies reveal a putative essential link between DNA modification and RNA methylation,and illustrate the epigenetic maps during human foetal organogenesis,which provide a foundation for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.

关 键 词：Human foetus Foetal organogenesis DNA 5hmC RNA m^(5)C Post-transcriptional regulation 

分 类 号：R563[医药卫生—呼吸系统]