Figure 1

KAP1 has an N-terminal tripartite motif (TRIM) containing an RBCC domain (ring finger, two B-box zinc-fingers and a coiled coil), a central HP1 (heterochromatin protein 1) domain and a C-terminal combination plant homeodomain (PHD) and bromodomain (B). These three domains have been shown to mediate nuclear localization, interaction with TFs, oligomerization and regulation of transcription.²¹ The RBCC domain interacts with the KRAB module present in the KRAB-C2H2 zinc-finger proteins (KZNF). In addition to the RBCC domain, every other subdomain of KAP1 contributes to the remodeling of chromatin on genomic loci targeted by the KRAB-containing TFs.⁹ For instance, the HP1-binding domain (PxVxL) interacts with HP1 family members, whereas the KAP1–HP1 complex has a role in silencing euchromatic and pericentric heterochromatic regions.²¹ The PHD and bromodomain interact with two chromatin-modifying enzymes: Mi2a and SETDB1, of which SETDB1 encodes a histone methyltransferase involved in histone methylation, gene silencing and transcriptional repression⁸