ZNF224: Structure and role of a multifunctional KRAB-ZFP protein

The Kruppel-like zinc finger protein ZNF224 was originally identified as the transcriptional repressor of the human aldolase A gene. ZNF224 transcriptional repression depends on interaction with the corepressor KAP-1 and recruitment of enzyme activities modifying chromatin, in accordance with repression mechanism of KRAB-ZFP family. Recently, the arginine methyltransferase PRMT5 was demonstrated to play a crucial role in the transcriptional ZNF224 repressor complex. An alternatively spliced isoform, ZNF255, arises from the ZNF224 gene. ZNF224 and ZNF255 have a distinct pattern of distribution within the cell and display a specific pattern of interaction with different molecular partners. These isoform-specific interactions seem to control different cellular pathways. These findings suggest that ZNF224 is a multifunctional protein and that alternative splicing, sub-cellular compartmentalization and isoform-specific interactions may modulate its activity.