Programming cell fates with synthetic SOX and OCT transcription factors (#44)
My laboratory studies how transcription factors (TFs) recognize DNA to ‘read’ the regulatory information encoded in mammalian genomes and direct cell fate decisions. We use structural modeling and quantitative biochemical assays to study TF dimerization on composite DNA elements enriched in cis-regulatory sequences. Further, by acquiring and analyzing next-generation sequencing datasets (ChIPseq and RNAseq) we aim to decipher the ‘enhancer code’ regulating gene activity. We specifically ask how combinations of lineage specifying TFs (including SOX2, OCT4, PAX6 and FOXA1 proteins) work together to execute gene expression programs. We utilize our insights to engineer synthetic TFs (sTFs) that program cell fates faster, more efficiently and in a more controlled fashion than their wild-type counterparts. I will discuss ongoing strategies to identify novel sTFs. Further, genome-wide studies monitoring how re-engineered Oct4 variants with re-balanced dimerization preferences direct reprogramming to pluripotency will be presented.
