The Kruppel-like zinc finger protein ZNF224 recruits the arginine methyltransferase PRMT5 on the transcriptional repressor complex of the aldolase A gene.

Gene transcription in eukaryotes is modulated by the coordinated recruitment of specific transcription factors and chromatin-modulating proteins. Indeed, gene activation and/or repression is/are regulated by histone methylation status at specific arginine or lysine residues. In this work, by co-immunoprecipitation experiments, we demonstrate that PRMT5, a type II protein arginine methyltransferase that monomethylates and symmetrically dimethylates arginine residues, is physically associated with the Kruppel-like associated box-zinc finger protein ZNF224, the aldolase A gene repressor.

Differential expression and cellular localization of ZNF224 and ZNF255, two isoforms of the Krüppel-like zinc-finger protein family.

We previously reported that ZNF224, a novel Krüppel-associated box-containing zinc-finger protein, represses aldolase A gene transcription by interacting with the KAP-1 co-repressor. Using northern blot and PCR procedures, we now demonstrate that the transcript encoding ZNF255 is a ZNF224 isoform and that the corresponding mRNAs are differentially expressed in human adult and foetal tissues. Moreover, transient transfection of recombinant ZNF224 and ZNF255 proteins and chromatin-immunoprecipitation assays indicate that ZNF224 binds the negative regulatory element of the aldolase A gene (AldA-NRE) and inhibits transcription more efficiently than ZNF255.

The Krüppel-like zinc-finger protein ZNF224 represses aldolase A gene transcription by interacting with the KAP-1 co-repressor protein.

Transcription factors belonging to the Krüppel-like zinc finger family of proteins participate in the regulation of cell differentiation and development. Although many of these proteins have been identified, little is known about their structure and function. We recently purified ZNF224, a new Krüppel-like zinc finger protein, that contains a Krüppel-associated box (KRAB) domain at the NH2 terminus, and 19 Cys2-His2 zinc-finger domains at the COOH terminus.