Jumonji and AT-rich interaction domain-containing protein 2 (JARID2)

Jumonji and AT-rich interaction domain-containing protein 2 (JARID2) is a non-enzymatic member of the jumonji family of proteins that serves as a critical cofactor of the Polycomb Repressive Complex 2 (PRC2). JARID2 facilitates recruitment of PRC2 to chromatin and modulates the activity of PRC2, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), resulting in transcriptional repression of target genes. In embryonic stem cells, full-length JARID2 is required for maintenance of pluripotency, while in lineage-committed cells, a truncated form predominates and is associated with activation of differentiation genes. JARID2 possesses nucleosome-binding activity and contains ARID and zinc finger domains for DNA binding, but has an inactive demethylase domain. Dysregulation of JARID2 and its interactions with the PRC2 complex has been implicated in cancer and developmental abnormalities. JARID2 remains indispensable for proper developmental gene regulation but has yet to be directly targeted by specific therapeutic drugs.

Other names

Protein JumonjiJARID2JMJJumonji/ARID domain-containing protein 2DIDDFjumonji homologjumonji-like protein

Inhibition or modulation of PRC2 complex activity; most drugs/experimental molecules target catalytic subunits of PRC2 (e.g., EZH2 inhibitors). Indirect modulation of JARID2 function via compounds that affect chromatin modifiers or disrupt protein-protein interactions within PRC2.