In metazoans, in order to respond to environmental stress, differentiate properly, and progress normally through the cell cycle, a eukaryotic cell needs a specific and coordinated gene expression program, which involves the highly regulated transcription of thousands of genes. This gene regulation is in large part controlled, in a tissue-specific manner, by the binding of transcription factors to noncoding genomic regions referred to as cis-regulatory modules (CRMs), activating or repressing gene expression by modulating the structure of the chromatin and therefore having a positive or negative effect on transcription regulation. CRMs activating gene expression are often referred to as transcriptional enhancers, whereas those repressing gene expression are referred to as transcriptional silencers.