# DECODING THE IMPACT OF TRANSPOSABLE ELEMENTS ON GENE REGULATION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $393,750

## Abstract

At least half of the human genome is derived from transposable elements (TEs). While some
investigations regard TEs as “parasitic” DNA, other studies suggest that TEs play a more constructive role
in genome evolution by providing raw material for new biological functions. TEs commonly harbor active cis-
regulatory elements that are occasionally co-opted during evolution to wire new gene regulatory networks.
TEs remain under-analyzed in high-throughput data because of methodological hurdles associated with
their repetitive nature. Thus, the impact of TEs on the regulation of the human genome, both in normal
development and disease, remains largely uncharacterized. We propose to develop advanced genomics
approaches to assess and clarify the impact of TEs in regulatory innovation, conservation, and in human
diseases. In Aim 1 we combine a novel statistical framework with massively parallel reporter gene assays
to understand TE sequence features that contribute to gene regulation. We will take advantage of the
repetitive nature of TEs to link sequence changes in different copies of TEs to epigenetic and functional
differences, and test their regulatory activities using a new genome integrated massive parallel reporter
gene assay. In Aim 2 we will extend the models developed in Aim 1 to understand the role of TEs in
shaping the 3D topology of the genome, which is intimately connected to genome function. We will quantify
the extent to which TEs underlie the conservation and/or divergence of genome topology across
mammalian species. In Aim 3 we will develop technologies to detect TE-gene fusions linked to disease. We
aim to detect cases where epigenetically de-repressed TEs initiate transcripts that splice into downstream
genes, resulting in TE-gene fusion chimeric RNA and protein products. We will develop tools to detect such
TE-gene fusion transcripts, and will adapt CRISPR-based genetic and epigenetic tools in order to
manipulate TEs, which will allow us to establish whether TEs play a causal role in this type of abnormal
gene activity. In Aim 4 we will test the hypothesis that epigenetic inhibitors commonly used for therapeutics
alter TEs’ epigenetic regulation. Through the aims of this proposal we hope to develop an understanding of
what sequence features drive the regulatory potential of TEs, and the modes of evolution followed by
different families of TEs during regulatory network evolution. Such an understanding will improve our picture
of regulatory network evolution by including the effects of TEs, a major class of fast evolving sequences that
have been largely ignored in functional genomics studies. The methods developed in this proposal will have
a high impact on the utility of data produced by consortia such as ENCODE, Roadmap, TCGA, and other
large-scale projects, which currently discard most TE derived sequences from their data. Such improvement
will in turn accelerate research into understanding the impact of TEs’ on normal gene regulati...

## Key facts

- **NIH application ID:** 10208924
- **Project number:** 5R01HG007175-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ting Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2014-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208924

## Citation

> US National Institutes of Health, RePORTER application 10208924, DECODING THE IMPACT OF TRANSPOSABLE ELEMENTS ON GENE REGULATION (5R01HG007175-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10208924. Licensed CC0.

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