Transcriptional repression - The cancer-chromatin connection

Mutations in the retinoblastoma (Rb) tumour-suppressor protein are implicated in many types of cancer. In healthy cells, Rb binds to the E2F protein, preventing the transcription of genes that would otherwise be activated by E2F. But in cancer cells, this repression is turned off, allowing the cells to enter the cell cycle. In an attempt to find out how Rb normally effects this repression, two groups have found that it binds to the histone deacetylase HDAC1, acting as a bridge to tether this protein to E2F. The HDAC1 protein therefore represses the E2F-regulated promoter, in an interaction that is mediated by Rb.