ZNF200

ZNF200 is a Krüppel-type zinc finger protein containing five C2H2 zinc finger motifs that functions as a nuclear scaffold linking chromatin-modifying enzymes to their substrates. ZNF200 interacts with the H3K9 methyltransferase G9a through three of its zinc finger domains and co-localizes with G9a in nucleoplasmic speckles (PMID:17584299). ZNF200 also binds PRMT3 via its C-terminal zinc fingers contacting PRMT3's N-terminal zinc finger domain, stabilizes PRMT3 against proteasomal degradation, promotes its nuclear translocation, and thereby increases global H4R3me2a histone marks (PMID:39513743).

1. 1998 Medium

   Cloning of ZNF200 established it as a Krüppel-type zinc finger gene with five C2H2 motifs, an alternatively spliced form, and preferential expression in testis, providing the molecular framework for subsequent functional studies.

   Evidence cDNA cloning, Northern blot, and genomic sequencing in human tissues

   PMID:9787081

   Open questions at the time

   • No functional role or binding partners identified
   • Expression data limited to Northern blot without protein-level confirmation
2. 2007 High

   Identification of G9a as a direct binding partner of ZNF200 established the first functional link between ZNF200 and histone methylation, with domain mapping showing that three of five zinc fingers mediate the interaction and co-localization placing both proteins in nuclear speckles.

   Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation from HEK293 cells, GST pull-down with deletion mapping, and fluorescence microscopy co-localization

   PMID:17584299

   Open questions at the time

   • Functional consequence of ZNF200–G9a interaction on H3K9 methylation not measured
   • No loss-of-function experiment to assess whether ZNF200 is required for G9a activity or localization
   • Endogenous interaction not confirmed with antibodies against native proteins
3. 2024 High

   Discovery of ZNF200 as a PRMT3 stabilizer and nuclear escort revealed a second chromatin-modifier partnership: ZNF200 inhibits PRMT3 proteasomal degradation, drives its nuclear accumulation, and thereby elevates global H4R3me2a, broadening ZNF200's role from a single interaction partner to a general adaptor for chromatin-modifying enzymes.

   Evidence Yeast two-hybrid, co-immunoprecipitation, GST pull-down with domain mapping, proteasome inhibition assays, nuclear fractionation, and H4R3me2a immunoblotting

   PMID:39513743

   Open questions at the time

   • Whether ZNF200's interactions with G9a and PRMT3 are simultaneous or mutually exclusive is unknown
   • In vivo phenotype of ZNF200 loss in model organisms not reported
   • Genome-wide chromatin targets of ZNF200-dependent methylation changes not mapped

• It remains unknown whether ZNF200 acts as a DNA-binding transcription factor through its zinc fingers, whether its partnerships with G9a and PRMT3 are coordinated to regulate specific genomic loci, and what physiological consequence ZNF200 deficiency has in vivo.
• No DNA-binding activity or target genes characterized
• No knockout or knockdown phenotype in animal models
• Potential role in testis where expression is highest remains unexplored