Patterns in the tapestry of chromatin-bound RB.

RB regulation of E2F is an important component of a highly conserved cell cycle machine, but the consequences of RB loss are mostly context-specific. ChIP-seq studies indicate that RB does not act exclusively at promoters but is also associated with enhancers and chromatin insulators. Cell cycle transitions alter the distribution of RB; when cells proliferate, RB redistributes away from promoters and toward enhancers. RB-binding sites in promoters are conserved; in contrast, RB-binding sites in nonpromoter regions are largely cell type-specific and are mostly independent of E2F. RB's cell type-specific interactions with enhancers and insulators may help to explain some of RB's context-specific activities and its noncanonical functions. The retinoblastoma protein (RB)-mediated regulation of E2F is a component of a highly conserved cell cycle machine. However, RB's tumor suppressor activity, like RB's requirement in animal development, is tissue-specific, context-specific, and sometimes appears uncoupled from cell proliferation. Detailed new information about RB's genomic distribution provides a new perspective on the complexity of RB function, suggesting that some of its functional specificity results from context-specific RB association with chromatin. Here we summarize recent evidence showing that RB targets different types of chromatin regulatory elements at different cell cycle stages. RB controls traditional RB/E2F targets prior to S-phase, but, when cells proliferate, RB redistributes to cell type-specific chromatin loci. We discuss the broad implications of the new data for RB research. [ABSTRACT FROM AUTHOR]