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Polymorphic 3D genome architecture mediated by transposable elements.

Harsh Shukla1, Yuheng Huang1, Yi Zita Gao1

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Transposable elements (TEs) introduce 3D genome structure variations by interacting with pericentromeric heterochromatin (PCH). This polymorphism impacts gene expression and evolution, driven by epigenetic marks like H3K9me3.

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Area of Science:

  • Genomics
  • Epigenetics
  • Evolutionary Biology

Background:

  • The three-dimensional (3D) genome folding is vital for gene regulation.
  • Individual variation in 3D genome structure and its functional/evolutionary impact are poorly understood.
  • Transposable elements (TEs) are a source of genomic variation and can interact with pericentromeric heterochromatin (PCH).

Purpose of the Study:

  • To investigate if polymorphic TE insertions drive variations in 3D genome structure.
  • To explore the role of TE-PCH interactions in shaping genome organization and function.
  • To understand the evolutionary implications of TE-mediated 3D genome organization.

Main Methods:

  • Deep-coverage Hi-C sequencing in two wild-type Drosophila strains.
  • Development of a Hi-C analysis framework for allelic comparisons of spatial interactions with PCH.
  • Analysis of TE presence/absence polymorphism and its association with PCH proximity.

Main Results:

  • Nearly 40% of strain-specific euchromatic TEs promote closer spatial proximity to PCH compared to TE-free alleles.
  • TE-PCH interactions are mediated by H3K9me3 enrichment, a chromatin-based mechanism.
  • Both centromere-proximal and telomere-proximal TEs can enhance PCH interactions, affecting adjacent gene expression.

Conclusions:

  • TEs contribute to polymorphic 3D genome organization by interacting with PCH.
  • This TE-driven structural variation influences genome function (gene expression) and evolution.
  • TEs involved in PCH interactions are evolutionarily young, suggesting selection against them.