| First Author | Laresgoiti U | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 22 | Pages | 10185-98 |
| PubMed ID | 24038359 | Mgi Jnum | J:211219 |
| Mgi Id | MGI:5574272 | Doi | 10.1093/nar/gkt821 |
| Citation | Laresgoiti U, et al. (2013) E2F2 and CREB cooperatively regulate transcriptional activity of cell cycle genes. Nucleic Acids Res 41(22):10185-98 |
| abstractText | E2F2 is essential for the maintenance of T lymphocyte quiescence. To identify the full set of E2F2 target genes, and to gain further understanding of the role of E2F2 in transcriptional regulation, we have performed ChIP-chip analyses across the genome of lymph node-derived T lymphocytes. Here we show that during quiescence, E2F2 binds the promoters of a large number of genes involved in DNA metabolism and cell cycle regulation, concomitant with their transcriptional silencing. A comparison of ChIP-chip data with expression profiling data on resting E2f2(-)(/)(-) T lymphocytes identified a subset of 51 E2F2-specific target genes, most of which are upregulated on E2F2 loss. Luciferase reporter assays showed a retinoblastoma-independent role for E2F2 in the negative regulation of these target genes. Importantly, we show that the DNA binding activity of the transcription factor CREB contributes to E2F2-mediated repression of Mcm5 and Chk1 promoters. siRNA-mediated CREB knockdown, expression of a dominant negative KCREB mutant or disruption of CREB binding by mutating a CRE motif on Mcm5 promoter, relieved E2F2-mediated transcriptional repression. Taken together, our data uncover a new regulatory mechanism for E2F-mediated transcriptional control, whereby E2F2 and CREB cooperate in the transcriptional repression of a subset of E2F2 target genes. |
