# Functional and evolutionary consequences of the epigenetic effects of transposable elements

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $249,000

## Abstract

PROJECT SUMMARY
Transposable elements (TEs) are genomic parasites that can negatively impact host viability and fertility.
Despite the detrimental effects of TEs, they constitute appreciable proportions of virtually all eukaryotic
genomes surveyed. Eukaryotic genomes can be cytologically divided into euchromatin and heterochromatin,
with the latter being tightly packaged DNA generally associated with suppressed expression. While the
heterochromatin of most species is infested with degenerated TEs, the proportions of host euchromatic
genomes that are occupied by potentially active TEs are remarkably different between species (e.g., human,
45%; Drosophila melanogaster, 5.4%). This proposal aims to understand the molecular and evolutionary
mechanisms contributing to the widely observed, but poorly understood, between-species differences in TE
content, which will be critical for the understanding of eukaryotic genome evolution and the genetics of
inherited diseases and cancers caused by TEs.
 Natural selection can remove deleterious TE insertions from populations, and variation in the strength
of selection is expected to result in differences in TE content between host genomes. Most previous work on
the deleterious effects of TEs has centered on the consequences of TE-induced physical disruption of DNA.
Instead, this proposal focuses on the largely unexplored epigenetic effects of TEs. Constitutive
heterochromatin has the potential to influence the epigenetic states of adjacent genes through cis-spreading of
repressive epigenetic marks as well as spatial interactions with other heterochromatic regions. In euchromatin,
active TEs can be silenced through host-directed enrichment of repressive epigenetic marks, which were also
observed to spread in cis into adjacent genes and thereby epigenetically impair gene function. By using
Drosophila as a model, this proposal will use a combination of Hi-C analysis and cell biological experiments to
investigate if euchromatic TEs epigenetically impact adjacent genes through spatial interactions with
constitutive heterochromatin, which will identify previously unknown epigenetic effects of TEs (Aim 1). Host
genotypes and environmental conditions are known to modulate the spreading of silencing marks from
heterochromatin to adjacent sequences. The influence of these host components on the epigenetic effects of
TEs in euchromatin will be tested (Aim 2). Finally, this proposal will use comparative functional genomics and
phylogenetic analysis to test the hypothesis that between-species variation of host components that modulate
TE's epigenetic effects contributes to different epigenetic effects of TEs, and ultimately divergent TE content
across the Drosophila phylogeny.

## Key facts

- **NIH application ID:** 10006836
- **Project number:** 5R00GM121868-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Grace Yuh Chwen Lee
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006836

## Citation

> US National Institutes of Health, RePORTER application 10006836, Functional and evolutionary consequences of the epigenetic effects of transposable elements (5R00GM121868-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10006836. Licensed CC0.

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