Thesis work by lab alumnus, Nathan Kopp, Ph.D., is out today in Human Molecular Genetics detailing the DNA-binding features and targets of two gene (products)–Gtf2i and Gtf2ird1–from the Williams Syndrome (WS) genomic region. Both appear to intersect topological domain boundaries and CTCF binding sites, suggesting a role in chromatin structure. Moreover, both bind at promoters of highly-conserved (mutation-intolerant) genes, including some associated with autism spectrum disorders. This intersection is especially interesting, as Williams Syndrome features a hypersocial phenotype, in stark contrast to the asocial nature of autism spectrum disorders.

Mouse behavior work spearheaded by Nathan and Kayla Nygaard revealed that loss of Gtf2ird1 increases Williams-like phenotypes, including marble burying (compulsive/anxious behavior, sometimes also considered defensive); impaired balance, consistent with motor dysregulation in WS; and sensitization to conditioned fear (a stronger Pavlovian response to a stimulus previously presented along with an aversive stimulus), consistent with general anxiety in WS.

This is an exciting capstone on Nathan’s productive Ph.D career in our lab. Congratulations to him and the rest of the team!

You can read the article here.