# The regulatory impact of transposable elements (TEs) on differential gene expression in closely related species during cellular differentiation

> **NIH NIH F31** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $37,995

## Abstract

Abstract
Environmental factors contribute to the susceptibility of developing heart disease, but the same factors do not
equally increase the disease risk for all people. Understanding how almost identical DNA between individuals
provides so much variation in physiological and pathological presentation is essential to predicting a person’s
risk of heart disease correctly. Differential gene regulation is a strong candidate for explaining these observed
variations. Transposable Elements (TEs) comprise fifty percent of primate genomes but have long been
considered “junk” DNA. However, recent studies have shown that TEs play a role in gene regulation in terminally
differentiated cells between humans and chimpanzees, whose genomes share 98% similarity. Other studies
have also demonstrated that differential silencing of TEs between humans and chimpanzees does not contribute
to differential gene expression between the species' induced pluripotent stem cells (iPSCs). A knowledge gap
exists regarding the developmental stage when TEs might begin to explain species-specific gene expression
differences. I hypothesize that TEs have played a significant role in generating differences between primates
through species-specific gene regulation throughout cellular differentiation. Aim 1 is to define the roles of TEs
in species-specific gene regulation as iPSCs differentiate into cardiomyocytes. I will differentiate and
collect human and chimpanzee iPSCs as they progress from pluripotency to mesoderm, cardiac mesoderm, and
cardiomyocytes. Cellular phenotypes will be resolved through RNA sequencing, and differential gene
expressions between species will be determined. To assess which regions of DNA have active (H3K27ac) and
repressive (H3K9me3) chromatin modifications, Cleavage Under Targets and Tagmentation (CUT&Tag) will be
performed in both species. I will overlap DNA regions with active and repressive histone modifications to the TE
annotation file, RepeatMasker, to identify TEs in regulatory proximity to differentially expressed genes. Aim 2 is
to discover the roles of TEs in differential gene expression between closely related species during the
early embryological event of mesoderm specification. Human and chimpanzee iPSCs will be differentiated
into the mesoderm, endoderm, and ectoderm lineages. The contribution of TEs to differences in early regulatory
events between species will be assessed through the approaches discussed above, comparing mesoderm to
the other germ layers to determine lineage-specific effects. Through the abovementioned project, I will gain skills
in iPSC cell culture, differentiation techniques, and assays to assess epigenetic gene regulation. I will also
develop expertise in utilizing computational approaches for processing RNA-sequencing data and developing
pipelines to compare expression and gene regulatory features across species, necessitating the identification of
orthologous regions and genes for direct comparison. These skills wi...

## Key facts

- **NIH application ID:** 10996765
- **Project number:** 1F31HL172519-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** John Dennis Hurley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $37,995
- **Award type:** 1
- **Project period:** 2024-09-30 → 2027-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996765

## Citation

> US National Institutes of Health, RePORTER application 10996765, The regulatory impact of transposable elements (TEs) on differential gene expression in closely related species during cellular differentiation (1F31HL172519-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10996765. Licensed CC0.

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