Variations in regulatory activity are frequently directly linked to genetic variation, as modifications in transcription factor binding result in modifications to the regulatory landscape . RNA polymerase II can transcribe any protein-coding gene. The information that determines whether a specific gene should be transcribed is partially present in cis on the DNA in the form of specific DNA sequences (motifs) and partly in trans on the DNA in the form of proteins called transcription factors (TFs) that recognize and bind to these specific motifs . Changes in TF binding, which can lead to coordinated changes in a diverse array of supporting regulatory mechanisms, can disproportionately influence changes in steady-state gene expression levels . Numerous transcription factors, each with multiple binding sites, equip enhancers with binding sites. In certain instances, the physical proximity between the enhancer and promoter directly influences gene expression, as these interactions only take place during gene expression .