Gene regulation is central to development and cellular differentiation, and erroneous gene expression is linked to many diseases including cancer. Gene regulatory information is encoded in the DNA sequences of genomic cis-regulatory elements called enhancers, which activate or repress transcription from their target genes’ core-promoters. Different transcription factors (TFs) bind to short recognition sites within enhancers - thus essentially reading the regulatory information contained in the enhancer sequence - and recruit cofactors (COFs), such as the Mediator complex or the acetyltransferase CBP/p300. Together, these regulatory proteins mediate RNA polymerase II (Pol II) recruitment and activation at core-promoters.