Description:

The Department of Biochemistry and Molecular Genetics welcomes you to attend a seminar by faculty candidate, Emma Farley, PhD, Assistant Professor, Department of Molecular Biology, UCSan Diego

Abstract:

Enhancers direct precise patterns of gene expression during development by interactions with transcription factors (TFs)1,2. To explore how the organization of transcription factor binding sites (TFBSs) within enhancers encodes this precision, we conducted a high-throughput screen testing 460,800 different organizations of ETS and GATA TFBSs for activity within developing embryos. We provide evidence that enhancer-specificity depends on the functional organization, or syntax, of TFBSs. Optimal syntax of TFBSs mediates robust but ectopic patterns of gene expression. Multiple overlapping syntax features within an enhancer encode activity. Too many syntax features, or individual syntax features that are too optimal, lead to loss of specificity. Tissue-specific enhancers have less optimal syntax, which is permissive to transcription but is dependent on the affinity of TFBSs. Enhancer grammar3, the interplay of sub-optimal syntax and affinity, encodes tissue-specificity. We use this grammatical principle to predict genomic enhancers and design synthetic enhancers that drive precise gene expression in response to pleiotropic factors. Our study uncovers how the complex language of enhancers encodes tissue-specificity, with far reaching applications for reading and writing gene expression.