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Widespread somatic L1 retrotransposition in normal colorectal epithelium

 Chang Hyun Nam  ;  Jeonghwan Youk  ;  Jeong Yeon Kim  ;  Joonoh Lim  ;  Jung Woo Park  ;  Soo A Oh  ;  Hyun Jung Lee  ;  Ji Won Park  ;  Hyein Won  ;  Yunah Lee  ;  Seung-Yong Jeong  ;  Dong-Sung Lee  ;  Ji Won Oh  ;  Jinju Han  ;  Junehawk Lee  ;  Hyun Woo Kwon  ;  Min Jung Kim  ;  Young Seok Ju 
 NATURE, Vol.617(7961) : 540-547, 2023-05 
Journal Title
Issue Date
Aging / genetics ; Carcinogenesis / genetics ; Colon* / metabolism ; Colorectal Neoplasms / genetics ; Colorectal Neoplasms / pathology ; DNA Transposable Elements* / genetics ; Embryonic Development / genetics ; Epigenomics ; Gene Frequency ; Genome, Human / genetics ; Genomics ; Humans ; Intestinal Mucosa* / metabolism ; Long Interspersed Nucleotide Elements / genetics ; Mosaicism ; Retroelements* / genetics
Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells1–11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12–14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime. © 2023, The Author(s).
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Oh, Ji Won(오지원) ORCID logo https://orcid.org/0000-0001-5742-5120
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