Transcription factors, enhancers and control of cell fate

Accurate gene expression is fundamental to life. Gene expression is controlled by transcription factors binding to regulatory elements in the genome (enhancers). Transcription factors operate in highly interconnected networks.

It is well established that groups of transcription factors cooperate to facilitate each other's access to DNA and bind to enhancers.

However, a fundamental question is how multiple transcription factors, once anchored to their target enhancer, cooperate to activate gene transcription. Are the multiple transcription factors bound to enhancers equivalent and therefore interchangeable? Or do they contribute different functions?

This project combines high-throughput and single locus-based approaches in tractable systems (human embryonic stem cells) with computational approaches to study how transcription factors function at cell type-specific enhancers and define their contributions to gene expression.

Results from this project will clarify how cell-type specific enhancers are selected and activated and how specific cells states are established, addressing a fundamental question in biology and paving the way for efficient cell reprogramming and the generation of specific cell types.