Figure 2. Genome engineering reveals locus‐specific transcriptional and architectural consequences of TAD boundary deletion and insertion.

(A) TAD or a sub‐TAD boundary deletion may lead to no overt alteration of chromatin architecture as seen at the Firre locus (Barutcu et al, ²⁰¹⁸), or to TAD and subTAD merging accompanied by either modest (Sox9/Kcjn2; Despang et al, ²⁰¹⁹) or considerable transcriptional changes (e.g., loss of insulated neighbourhoods and oncogene activation; Hnisz et al, ²⁰¹⁶), or aberrant activation of genes as, for example in the vicinity of otherwise insulated globin genes (Hanssen et al, ²⁰¹⁷). (B) Ectopic insertion of a boundary element may lead to no change in the architecture of the recipient locus (Barutcu et al, ²⁰¹⁸). When considering other CBS, boundaries can still be formed despite the deletion of the CBS. Depending on whether the ectopic boundary is inserted far or close to a Nipbl cohesin loader binding site, the boundary may form stripes (Redolfi et al, ²⁰¹⁹). The contribution of distinct elements making up the boundary depends on the intrinsic features of the target locus. At one location, a boundary composed of a CBS site and a housekeeping gene promoter depends on both elements, while at another location CTCF appears less crucial for boundary formation (Zhang et al, ²⁰²⁰).