Zinc finger MYND domain-containing protein 11 (ZMYND11)

Zinc finger MYND domain-containing protein 11 (ZMYND11) is a nuclear chromatin reader and transcriptional regulator. It specifically recognizes the trimethylation on lysine 36 of histone variant H3.3 (H3.3K36me3) via its tandem PHD-bromo-PWWP domains and acts as an “epigenetic gatekeeper” by regulating RNA polymerase II elongation and repressing cryptic transcription[2][3][6]. Beyond direct transcriptional repression, ZMYND11 serves as a multifaceted tumor suppressor by integrating chromatin state with RNA processing, splicing regulation, and interactions with oncogenic transcription factors and viral proteins (e.g., adenoviral E1A, Epstein–Barr virus EBNA2)[2][3][5]. Recent studies reveal a noncanonical function: ZMYND11, through its MYND domain, binds arginine-methylated HNRNPA1 and retains it in the nucleus, thereby preventing cytoplasmic stress granule formation and restraining tumor progression; this interaction can be disrupted with PRMT5 inhibitors, making ZMYND11 and the ZMYND11-HNRNPA1 axis promising cancer therapeutic targets and biomarkers[1][4]. Loss or reduction of ZMYND11 is implicated in aggressive cancers (breast, glioblastoma, prostate, hematological malignancies) and certain neurodevelopmental syndromes[2][4]. Mutations or gene fusions involving ZMYND11 are linked to altered chromatin modification landscapes and oncogenic transcription programs[2][3]. Thus, ZMYND11 is a critical integrator of epigenetic, transcriptional, and RNA splicing regulation in both normal development and disease contexts.

Other names

BRAM1BS69Adenovirus 5 E1A-binding proteinBone morphogenetic protein receptor-associated molecule 1MRD30

Disruption of ZMYND11-HNRNPA1 interaction via arginine methyltransferase inhibition (e.g., PRMT5 inhibitors)[1][4] Modulation of epigenetic readout, affecting elongation and splicing