Guided activation as a model for transcription factor networks determining cell fate

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The hundreds of different cell types in our body contain the same genetic instructions but produce different proteins because they express different genes. Gene expression is controlled by a class of proteins, called transcription factors (TFs). Therefore, TFs determine the differences in cell types and, when malfunctioning, cause a wide range of disease states. TFs recognize precise sequences in the genome to find their target genes. It is well established that TFs access their target genes much more efficiently when they operate in groups, but we still do not understand how these clusters of TFs, once bound to their target sequences in the genome, activate gene expression. We will address this fundamental question in biology through state-of- the-art experimental technologies and computational methods. Collectively, these results will provide new insight into how cell states are established, with direct relevance for efficient cell reprogramming and the generation of specific cell types.