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. Moreover, chromatin immunoprecipitation assays show that PRMT5 is recruited to the L-type aldolase A promoter and that methylation of the nucleosomes that surround the L-type promoter region occurs in vivo on the arginine 3 of histone H4. Consistent with its association to the ZNF224 repressor complex, the decrease of PRMT5 expression produced by RNA interference positively affects L-type aldolase A promoter transcription. Finally, the alternating occupancy of the L-type aldolase A promoter by the ZNF224-PRMT5 repression complex in proliferating and growth-arrested cells suggests that these regulatory proteins play a significant role during the cell cycle modulation of human aldolase A gene expression. Our data represent the first experimental evidence that protein arginine methylation plays a role in ZNF224-mediated transcriptional repression and provide novel insight into the chromatin modifications required for repression of gene transcription by Kruppel-like associated box-zinc finger proteins.
Cesaro
Elena
E
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini 5, Napoli 80131, Italy.
De Cegli
Rossella
R
Medugno
Lina
L
Florio
Francesca
F
Grosso
Michela
M
Lupo
Angelo
A
Izzo
Paola
P
Costanzo
Paola
P
D001120:Arginine / Q000737:chemistry; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry* / Q000235:genetics*; D017353:Gene Deletion; D006657:Histones / Q000737:chemistry; D006801:Humans; D008745:Methylation; D009154:Mutation; D011496:Protein Methyltransferases / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D012097:Repressor Proteins / Q000502:physiology*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; C470003:ZNF224 protein, human; D001120:Arginine; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D005634:Fructose-Bisphosphate Aldolase