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LINE-1 transcription activates long-range gene expression.
Li, Xiufeng; Bie, Luyao; Wang, Yang; Hong, Yaqiang; Zhou, Ziqiang; Fan, Yiming; Yan, Xiaohan; Tao, Yibing; Huang, Chunyi; Zhang, Yongyan; Sun, Xueyan; Li, John Xiao He; Zhang, Jing; Chang, Zai; Xi, Qiaoran; Meng, Anming; Shen, Xiaohua; Xie, Wei; Liu, Nian.
Affiliation
  • Li X; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Bie L; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Wang Y; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Hong Y; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Zhou Z; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Fan Y; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Yan X; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Tao Y; Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
  • Huang C; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Zhang Y; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Sun X; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Li JXH; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Zhang J; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Chang Z; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Xi Q; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Meng A; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Shen X; Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
  • Xie W; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Liu N; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. liunian88@tsinghua.edu.cn.
Nat Genet ; 56(7): 1494-1502, 2024 Jul.
Article in En | MEDLINE | ID: mdl-38849613
ABSTRACT
Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR-Cas9 screening using a reporter driven by the L1 5' UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Long Interspersed Nucleotide Elements / CRISPR-Cas Systems Limits: Animals / Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2024 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Long Interspersed Nucleotide Elements / CRISPR-Cas Systems Limits: Animals / Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2024 Document type: Article Affiliation country: China