Fig. 2

Chromosome partitioning into TADs reflects genome partitioning into regulatory domains delimiting zones of enhancer influence. Conventional concept of genomic domain implies that the entire genome is partitioned into non-overlapping parts (domains) containing gene clusters and regulatory regions (a), and demarcated with insulators preventing cross-talk between regulatory systems of the adjacent domains. According to current views, zones of enhancer influence (regulatory domains) largely overlap with TADs (b) that spatially confine communication between genes and enhancers located within adjacent regulatory domains. Deletion of TAD boundary leads to TAD fusion and, consequently, to fusion of corresponding regulatory domains resulting in abnormal enhancer-promoter communication and transcription dysregulation (c)