Sign in Subscribe
University of California

Uncovering the Regulatory Grammar of Non-Coding Genes through Short Tandem Repeats

Strategic Insights

— 1 min read

Researchers at the University of California have published a new study on the impact of short tandem repeats (STRs) on gene expression. The study reveals that genetic variation at thousands of STRs has a significant association with gene expression and other molecular phenotypes in humans. Using massively parallel reporter assays (MPRA), the researchers optimized a framework to study the impact of variation in repeat copy number on expression and identified 1,366 loci with significant associations between repeat copy number and expression.

Key Takeaways:

  • The study found that genetic variation at thousands of STRs has a statistically significant association with gene expression and other molecular phenotypes in humans.
  • The researchers used MPRA to study the impact of variation in repeat copy number on expression and identified 1,366 loci with significant associations between repeat copy number and expression.
  • The study revealed that the repeat unit sequence is the primary driver of differences in the relationship between copy number and expression across loci.
  • The researchers observed that a subset of STRs in their library show expression levels that are tightly linked with predicted DNA secondary structure formation.
  • The study provides a framework for understanding how STRs shape gene expression and establishes STRs as a critical component of the non-coding regulatory grammar.

Statistics:

  • 30,516 promoter-proximal STR loci were analyzed in the study.
  • 3-4 variants with differing repeat copy numbers were tested for each locus in HEK293T cells.
  • 1,366 loci with significant associations between repeat copy number and expression were identified.
  • The study observed that the repeat unit sequence is the primary driver of differences in the relationship between copy number and expression across loci.
  • 200-300 perturbations were performed for each of the 300 loci with the strongest signals.

Sources:

  • Systematic evaluation of the impact of promoter proximal short tandem repeats on expression (bioRxiv, 2025)
  • Lingzhi Zhang, Dept. of Medicine, University of California, San Diego, La Jolla, California 92093, United States
  • Additional authors for this research include Xuan Zhang, Ellice Wang, Susan Benton, Eduardo Modolo, Mikhail Maksimov, Sharona Shleizer-Burko, Qingqing Gong, Catherine Wang, Michael Lamkin, Eric Mendenhall, Melissa Gymrek and Alon Goren.

Read more