Figure 2. Topological domains and multigene complexes. (A) Chromosomes are organized into subchromosomal domains, referred to as TADs. CTCF, a sequence-specific DNA-binding protein, binds to consensus sites (CS) that frequently flank genes.²⁴ At CS sites, the multiprotein cohesin ‘ring-like’ complex (including the Smc1-Smc3 heterodimer, Rad21 and Scc3/SA1/SA2) is loaded onto chromatin by Nipbl. The mediator complex may also be recruited to CTCF and/or cohesin occupied chromatin to stabilize loop topology, and regulate transcription initiation and elongation.²¹ (B) Enhancer-promoter and promoter-promoter interactions in a single multigene complex. eRNA may possibly hold together the entire multigene complex.