ZNF618

ZNF618 is a chromatin-associated zinc finger protein that functions as a regulator of UHRF2-dependent 5-hydroxymethylcytosine (5hmC) reading (PMID:27129234). ZNF618 is recruited to 5hmC-enriched genomic loci through its first two zinc fingers, in a manner independent of its protein partners, and physically and selectively associates with UHRF2 but not its paralog UHRF1 (PMID:27129234). By controlling the chromatin localization of UHRF2, ZNF618 enables UHRF2 to function as a specific 5hmC reader in vivo (PMID:27129234). Beyond this interaction and its role in directing UHRF2 to chromatin, no further mechanistic detail has been characterized in the available corpus.

1. 2016 Medium

   Established that ZNF618 is a chromatin-targeting factor that confers UHRF2 its localization at 5hmC-rich loci, resolving how UHRF2 acts as a specific 5hmC reader in cells.

   Evidence Co-immunoprecipitation showing selective ZNF618-UHRF2 (not UHRF1) interaction, zinc-finger domain-deletion mapping of chromatin targeting, and ChIP-based co-localization at 5hmC loci in cells

   PMID:27129234

   Open questions at the time

   • Single-lab study without independent replication of the interaction specificity
   • No structural model of the ZNF618 zinc fingers engaging chromatin or 5hmC
   • Downstream functional/transcriptional consequences of UHRF2 mislocalization upon ZNF618 loss not defined

• Whether ZNF618 directly recognizes 5hmC or is targeted by another chromatin feature, and the biological pathways downstream of the ZNF618-UHRF2 axis, remain unknown.
• Direct DNA/5hmC-binding specificity of the ZNF618 zinc fingers not biochemically defined
• Physiological and developmental roles of ZNF618 uncharacterized