During quiescence, the DREAM complex represses G1/S and G2/M gene expression. In mammalian systems, chromatin-immunoprecipitation (ChIP) studies have revealed that DREAM components are found together at promoters of genes that peak in G1/S or G2/M phase. Abrogation of the DREAM complex on the other hand, led to increased expression of E2F regulated genes normally repressed in the G0 phase. Contrary to mammalian cells, the fly dREAM complex was found at almost one-third of all promoters, which may reflect a broader role for dREAM in gene regulation, such as programmed cell death of neural precursor cells.
Docking of the DREAM complex to promoters is achieved by binding of LIN-54 to regions known as cell cycle genes homology region (CHR). These are specific sequence of nucleotides that are commonly found in the promoters of genes expressed during late S phase or G2/M phase. Docking can also be achieved via E2F proteins binding to sequences known as cell cycle-dependent element sites (CDEs). Some cell cycle dependent genes have been found where both CHRs and CDEs are in proximity to one another. Because p130-E2F4 can form stable associations with the MuvB complex, the proximity of CHRs to CDEs suggests that affinity of binding of the DREAM complex to target genes is cooperatively improved by association with both the binding sites.
When DREAM is docked onto the promoter, p130 is bound to LIN52, and this association inhibits LIN52 binding to chromatin modifier proteins. Therefore, unlike RB-E2F, the DREAM complex is unlikely to directly recruit chromatin modifiers to repress gene expression, although some associations have been suggested. DREAM complex may instead down-regulate gene expression by affecting nucleosome positioning. Compacted DNA at transcription start sites inhibit gene expression by blocking the docking of RNA polymerase. In worms for example, loss of a MuvB complex protein, LIN35, leads to loss of repressive histone associations and high expression of cell cycle dependent genes. However, direct evidence for the link between repressive histones and the DREAM complex remains to be elucidated.