Pygopus family PHD finger 2 (PYGO2)

Pygopus family PHD finger 2 (PYGO2) is a nuclear chromatin effector protein and transcription co-activator that plays an essential role in the Wnt/β-catenin signaling pathway by facilitating the transcription of Wnt target genes. PYGO2 contains a conserved PHD (plant homeodomain) finger, uniquely capable of binding both methylated histone H3 (notably H3K4me2/3) and the co-factors BCL9/B9L, linking chromatin modification states to transcriptional activation complexes. Widely expressed during embryogenesis with higher abundance in tissues undergoing rapid development, PYGO2 is required for normal organogenesis, lens development, and kidney morphogenesis in mammals. Overexpression and dysregulation of PYGO2 are associated with cancer progression and poor prognosis, especially in gliomas and hormone-refractory prostate cancer, making it a potential biomarker and therapeutic target. Therapeutic modulation is challenging due to its role as a broad epigenetic regulator influencing numerous gene programs in both normal and malignant contexts.

Other names

Pygopus homolog 2PP79101190004M21Rikpygopus 2PYGO2

Targeted inhibition of chromatin binding or protein-protein interaction domains (e.g., PHD finger disruption) and modulation of Wnt/β-catenin pathway activity.