Expression data from WT, E2f8 KO, Rb KO and Rb;E2f8 DKO spleen Ter19+CD71high sorted cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52157 | GEO | 2014/05/30
SECONDARY ACCESSION(S): PRJNA227047
REPOSITORIES: GEO
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Project description:To understand molecular mechanisms underlying the synergy of Rb loss and E2F8 loss, we used gene expression profiling to assess molecular changes in Mx1-Cre-mediated knockout (KO) mice using RNA isolated from sorted Ter119+CD71high Erythroblasts. The top four upregulated and enriched pathways in the DKO mice included DNA replication, DNA damage response, DNA repair, and RNA processing. Interestingly, the majority of upregulated genes in the enriched sections of the four shared pathways contain E2f binding site(s) in their promoters, suggesting that Rb and E2F8 largely repress those genes through the E2f binding sites. Collectively, our data suggest that Rb and E2F8 co-regulate E2F-responsive genes. Spleen Ter119+CD71high cells were sorted from WT, E2f8 KO, Rb KO and E2f8;Rb DKO mice
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Project description:E2F transcription factors are central regulators of cell cycle progression and cell fate decisions in mammalian cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. E2F4 often represents the predominant E2F activity in cells. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. Importantly, this role for E2F4 is completely independent of the RB family. Accordingly, an unbiased analysis of the E2F4 interactome shows that E2F4 functionally interacts with chromatin regulators associated with gene activation in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that reveal novel insights into the biology of rapidly dividing cell types.
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Project description:The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity. We used microarrays to compare global profiles of gene expression and distinct responses of wildtype and Rb null MEFs in response to cisplatin. Keywords: genotype and cisplatin treatment
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