• Author
    Dadmehr Yaghoubi
  • Discovery PI

    Dr. Tamer Sallam

  • Project Co-Author

  • Abstract Title

    Experimental characterization of promoter short-tandem-repeat (STR) variants regulating cardiometabolic gene expression

  • Discovery AOC Petal or Dual Degree Program

    Basic, Clinical, & Translational Research

  • Abstract

    Background: Short tandem repeats (STRs) are highly polymorphic regulatory elements enriched in human gene promoters, where length variation can modulate transcription factor binding, chromatin architecture, and gene expression. Despite their abundance and established role as expression quantitative trait loci, the functional impact of promoter STR variation in cardiometabolic genes remains poorly characterized.

    Methods: Promoter fragments containing distinct STR alleles from four cardiometabolic candidate genes (CERS6, IRX3, SCAP, and AGTRAP) were cloned upstream of a firefly luciferase reporter and transcriptional activity was assessed using a dual luciferase assay in mammalian cells.

    Results: Of the four loci tested, IRX3 exhibited differential transcriptional activity across STR variants. The remaining three genes did not show significant allele-dependent differences under these conditions.

    Conclusions: These findings provide preliminary evidence that promoter STR length variation at IRX3 may influence transcriptional output. However, as the reporter system lacks native chromatin context and distal regulatory architecture, validation at the endogenous locus is necessary. Ongoing work is employing CRISPR/Cas9 editing to introduce distinct STR alleles in a haploid cell line (HAP1) to directly assess allele-specific gene expression.

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