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

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

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

Author: Xiao HAN ¹ ; Jia GUO ¹ ; Mengke WANG ² ; Nan ZHANG ¹ ; Jie REN ³ ; Ying YANG ⁴ ; Xu CHI ³ ; Yusheng CHEN ⁵ ; Huan YAO ⁵ ; Yong-Liang ZHAO ² ; Yun-Gui YANG ⁶ ; Yingpu SUN ⁷ ; Jiawei XU ⁸
Author Information

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; University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China.
3. Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.
4. Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
5. Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
6. Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: ygyang@big.ac.cn.
7. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: fccsunyp@zzu.edu.cn.
8. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: fccxujw@zzu.edu.cn.
Publication Type:Journal Article
Keywords: DNA 5hmC; Foetal organogenesis; Human foetus; Post-transcriptional regulation; RNA m(5)C
MeSH: Humans; DNA Methylation; RNA; Epigenesis, Genetic; DNA/genetics*; Basic Helix-Loop-Helix Transcription Factors/genetics*
From: Genomics, Proteomics & Bioinformatics 2023;21(4):805-822
CountryChina
Language:English
Abstract: 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 (m⁵C) 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 m⁵C-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 for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.