Figure 1.

Increasing complexity in transcriptional control. (A) Transcription factors (TFs, red circle) and components of the transcription machinery (TM, red hexagon), such as RNA polymerase II and transcriptional activators like the Mediator complex, assemble at the promoter (P, blue), upstream of the gene body (gray). (B) TFs bind to enhancer elements (E, green), giving rise to temporal and tissue-specific gene regulation by interaction with a disjoint promoter element. (C) Multiple enhancers modulate the transcriptional activity of a promoter, often over large genomic distances. (D) CREs organized in nuclear space forming a three-dimensional gene locus, interacting with various factors (red). (E) Topologically associating domains (TADs) are thought to encapsulate such three-dimensional structures, forming a network of enhancer–promoter interactions. TADs are often demarcated by insulators (Ins, yellow).