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Analysis of LINE-1 Retrotransposition at the Single Nucleus Level
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LINE-1 transcription activates long-range gene expression.

Xiufeng Li1, Luyao Bie1, Yang Wang1

  • 1Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

Nature Genetics
|June 7, 2024
PubMed
Summary

Long interspersed nuclear elements (LINE-1 or L1) activate distant genes. L1 elements are crucial for mammalian zygotic genome activation (ZGA), with L1 knockdown causing developmental arrest.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Developmental Biology

Background:

  • Long interspersed nuclear elements (LINE-1 or L1) comprise 17% of the human genome.
  • The precise control and function of L1 elements in gene regulation remain largely unknown.

Purpose of the Study:

  • To investigate the role of L1 transcription in regulating long-range gene expression.
  • To identify genes that control L1 expression and understand L1's impact on distant genes.

Main Methods:

  • Genome-wide CRISPR-Cas9 screening using an L1 5' UTR reporter in human cells.
  • Analysis of physical interactions between L1 elements and distal target genes.
  • L1 knockdown experiments in mouse embryos.

Main Results:

  • L1 transcription was found to activate gene expression over long genomic distances.
  • Knockout of regulatory genes significantly altered L1 expression and impacted distant gene expression.
  • L1 elements physically interact with distal genes, with interaction strength correlating to L1 activity.
  • L1 elements activate genes essential for zygotic genome activation (ZGA).

Conclusions:

  • L1 elements play a critical role in activating long-range gene expression.
  • L1 regulation is essential for mammalian zygotic genome activation (ZGA).
  • Disruption of L1 function leads to developmental arrest in mouse embryos.