E2F and RB proteins regulate the expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. Recent studies indicate that they function as part of an evolutionarily conserved multiprotein complex termed dREAM/ DREAM/LINC. Here we characterize the role of the Drosophila complex, dREAM, in the regulation of differentiation-specific E2F target genes in actively proliferating cells. These genes are regulated differently from cell cycle-related E2F targets, they do not depend on E2F activation, and E2F/RB repression is maintained throughout the cell cycle. In proliferating cells, their repression is dependent on dREAM. We find that dREAM plays a dual role in their regulation. First, it is required for the stability of the repressive dE2F2/RBF complexes at their promoters during S phase. Second, we find that dREAM is indispensable for both transcriptional repression mechanisms employed at these genes. Both cell division and exit from active proliferation cycles are integral parts of the development of multicellular organisms and are orchestrated by transcription factors that regulate spatiotemporal expression of specific sets of target genes. The E2F and RB families of transcription factors are critical regulators of these processes, and E2F/RB activity is altered in many human tumors (5,7,9,31,40).The E2F/RB pathway was first studied in the context of G 1 /S control (6, 9, 37). E2F proteins can be subdivided into repressors and activators of transcription. RB family members, also known as pocket proteins, negatively regulate E2F activity in two ways. Binding to activator E2Fs inhibits E2F transactivation. When bound to repressor E2Fs, they recruit transcriptional corepressors such as histone deacetylases (HDACs) or histone methyltransferases (HMTs) to inhibit expression of genes required for cell cycle progression (11). Cyclin-dependent kinases (CDKs) phosphorylate pocket proteins during cell cycle progression, thereby disrupting E2F-RB interactions. This results in both the relief of E2F/RB-mediated repression and the release of transcriptionally active E2F that triggers entry into S phase.It is now clear that E2F/RB functions extend beyond controlling S-phase entry. Biological activities for the pathway are inferred from both functional studies in mammals and other model organisms and through the identification of a vast network of target genes (2,9,19,34,39), including the control of the G 1 /S and G 2 /M transitions of the cell cycle, checkpoint control, DNA repair and recombination, apoptosis, differentiation, and development. How are all these diverse activities regulated? One answer may lie in the composite nature of the E2F/RB network; there are eight E2F factors in mammals, five of which can associate with three different pocket proteins. Individual E2F/RB complexes could perform distinct tasks and regulate different sets of genes in response to various signals. This idea is supported by several lines of evidence (9) and references therein.Another answer might be prov...

The recent decade witnessed an increase in CHM research activities and CHM English publications. Based on common problems identified in publications on CHM animal studies, we have proposed a checklist that could help in preliminary selection of publications lacking the most common problems and thus would be useful for a quick search of reproducible CHM regimens that are likely to be effective in a given context. The second application of this checklist is to help avoid the most common problems when designing experiments.