E2Fdriven

E2Fdriven refers to cellular programs, gene expression patterns, or phenotypes that are primarily regulated by the E2F family of transcription factors. The E2F family controls transcription of genes required for DNA replication and cell cycle progression from G1 to S phase, and its activity is tightly regulated by the retinoblastoma (RB) protein and its family members. When RB is hypophosphorylated, E2F factors are bound and inhibited; phosphorylation by cyclin-dependent kinases releases E2F, enabling transcription of S-phase genes. E2Fdriven states thus reflect active cell cycle entry and DNA replication programs.

Within the E2F family, E2F1-3 act primarily as transcriptional activators in complex with DP proteins, whereas E2F4-5 and some contexts recruit pocket proteins to repress transcription. The E2F-driven transcriptional program includes genes such as MCM2-7, PCNA, cyclins E and A, CDC6, and other components essential for DNA synthesis. In addition to promoting proliferation, E2F1 also participates in apoptosis under cellular stress, linking growth control to cell fate decisions.

Clinically, E2F-driven programs are often upregulated in cancers due to RB pathway disruption, contributing to uncontrolled proliferation. E2F-driven gene expression signatures are used in genomic analyses to assess proliferative status and tumor aggressiveness. Researchers employ methods such as ChIP-seq, RNA-seq, and gene set enrichment analysis to identify E2F targets and to define E2F-driven regulatory networks in development and disease.

Terminology: E2Fdriven is used to describe gene sets or cellular states characterized by E2F activity, rather than a single gene. The term emphasizes the regulatory influence of E2F transcription factors on broad suites of S-phase and growth-related genes.