STRs are a case study in the importance of sequence context and low-affinity binding! We hope our work inspires others to think beyond TF motifs! (9/11)

By analyzing published protein-binding microarray data, we predict that 90% of eukaryotic TFs bind at least one type of STR above background, suggesting that STRs (which are enriched in enhancers!) function as regulatory sequences. (8/11)

Kinetic measurements and modeling work from Emil Marklund and Julia Schaepe show that STRs primarily alter apparent association rates (k_on), perhaps affecting TF target search. (7/11)

What part of the TF is responsible for recognizing STRs? We made truncation mutants and single-residue substitutions of TFs and show that the DNA-binding domain directly recognizes STRs. (5/11)

Using partition function models from statistical mechanics, we show that STRs are low-affinity sites that maximize the number of binding microstates.
 
And we can apply these models to vastly improve binding predictions for any arbitrary TF and DNA sequence! (4/11)

Using high-throughput microfluidic binding assays, we showed that STRs can alter transcription factor binding affinities to a surprisingly large degree, up to 70-fold!
 
And here's the weird part: the STRs don't need to resemble high-affinity motifs to affect binding. (3/11)

Short tandem repeats (STRs) are enriched in eukaryotic regulatory elements and are known to alter gene expression. STR polymorphisms have also been associated with schizophrenia, Crohn's disease, and autism.
 
But the underlying mechanism has remained mysterious! (2/11)