ZNF200

ZNF200 is a nuclear C2H2-type zinc finger protein that acts as a scaffold and regulator of histone-modifying enzymes (PMID:17584299, PMID:39513743). It binds the H3K9 methyltransferase G9a through a region encompassing three of its five tandem zinc finger domains and co-localizes with G9a as discrete nucleoplasmic speckles (PMID:17584299). Through its C-terminal zinc finger regions, ZNF200 also binds the N-terminal zinc finger domain of the arginine methyltransferase PRMT3, stabilizing PRMT3 against proteasomal degradation and promoting its nuclear translocation, which drives a global increase in asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) (PMID:39513743). The encoding gene comprises five C2H2 zinc finger motifs distributed across four exons on chromosome 16p13.3 and is expressed predominantly in testis (PMID:9787081). Beyond these protein-protein interactions with G9a and PRMT3, the direct DNA-binding targets and broader physiological role of ZNF200 have not been characterized in the available corpus.

1. 1998 Medium

   The first question was the basic molecular identity of ZNF200, answered by defining it as a tandem C2H2 zinc finger protein with a testis-restricted expression pattern, establishing it as a candidate sequence-specific nucleic-acid- or protein-binding factor.

   Evidence cDNA cloning, intron-exon mapping, and Northern blot across tissues

   PMID:9787081

   Open questions at the time

   • No DNA-binding target or biochemical activity identified
   • Functional role of testis-enriched expression unaddressed
2. 2007 Medium

   The first functional partner was identified, linking ZNF200 to chromatin regulation by showing it binds the H3K9 methyltransferase G9a and co-localizes with it in nuclear speckles, implicating ZNF200 in repressive histone methylation machinery.

   Evidence Yeast two-hybrid, reciprocal Co-IP from HEK293 extracts, GST pull-down domain mapping, and immunofluorescence co-localization

   PMID:17584299

   Open questions at the time

   • No functional readout of the ZNF200-G9a complex on chromatin or transcription
   • Single-lab interaction without independent replication
   • Whether ZNF200 modulates G9a activity unknown
3. 2024 Medium

   A second enzyme partner established a mechanistic output: ZNF200 binds PRMT3, protects it from proteasomal degradation, and promotes its nuclear import, thereby increasing H4R3me2a — defining ZNF200 as a stabilizing scaffold that channels arginine methyltransferase activity into the nucleus.

   Evidence Yeast two-hybrid screen, Co-IP, GST pull-down, molecular docking, proteasomal degradation assay, nuclear fractionation, and H4R3me2a immunoblot

   PMID:39513743

   Open questions at the time

   • No independent replication
   • Genomic loci where ZNF200-PRMT3-driven H4R3me2a acts not mapped
   • Functional/phenotypic consequence of altered H4R3me2a not established

• Whether ZNF200's two documented partnerships (G9a and PRMT3) act in a common pathway, and whether its zinc fingers confer sequence-specific DNA binding to direct these enzymes to target loci, remains unresolved.
• No direct DNA target identified
• Integration of G9a and PRMT3 functions not tested
• No in vivo or disease phenotype established