Yin Yang 1 transcription factor (YY1)

Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins and encoded by the YY1 gene in humans. YY1 can act as either a transcriptional repressor or activator, integrating signals to modulate gene expression for processes such as cell proliferation, differentiation, apoptosis, DNA repair, and splicing. It functions through direct DNA binding, recruitment of chromatin remodeling complexes, and regulation of enhancer–promoter chromatin architecture. Dysregulation or overexpression of YY1 is implicated in the progression of several cancers, contributing to tumor proliferation, invasion, drug resistance, and poor prognosis. YY1 is also critical in development, with mutations associated with neurodevelopmental disorders like Gabriele-DeVries syndrome. YY1 interacts with numerous cofactors, including p300, HDACs, polycomb group proteins, MYC, and others. While preclinical studies have shown that YY1 inhibition can reduce tumor growth and sensitize tumors to therapy, challenges such as drug specificity, potential toxicity, and difficulty achieving selective inhibition over the homologous YY2 protein remain. No approved drugs directly target YY1 in clinical use, but it is considered a promising, albeit complex, therapeutic target for cancer and possibly other diseases.

Other names

Transcriptional repressor protein YY1INO80SYY-1NF-E1DELTAUCRBPYIN-YANG-1Delta transcription factorINO80 complex subunit SGADEVSYin and Yang 1 protein

Inhibition of YY1 expression (e.g., small molecules, RNAi): induces tumor cell apoptosis, blocks proliferation, may sensitize to chemotherapy. Modulation of YY1-regulated pathways (e.g., COX-2, EGFR, PD-L1): affects tumor growth, immune evasion.