E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family
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ABSTRACT:
PROVIDER: PRJNA431650 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6513310_1.fastq.gz | Fastqsanger.gz | |||
| SRR6513310_2.fastq.gz | Fastqsanger.gz | |||
| SRR6513301_1.fastq.gz | Fastqsanger.gz | |||
| SRR6513301_2.fastq.gz | Fastqsanger.gz | |||
| SRR6513311_1.fastq.gz | Fastqsanger.gz |
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Project description:E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in 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. 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. This role for E2F4 is independent of the RB family. Accordingly, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells.
2019-04-25 | GSE109684 | GEO
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.
2019-04-26 | PXD008796 | Pride
Project description:E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in 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. 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. This role for E2F4 is independent of the RB family. Furthermore, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells.
| S-EPMC6610666 | biostudies-literature
Project description:Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues. Experiment Overall Design: In one experiment, embryonic Day 13.5 placentas from wild-type and Rb -/- knock-out mice were compared. In the second experiment, embronic day 11.5 placentas from wild-type and Rb -/-;E2f4 -/- double knock-out mice were compared.
2009-06-24 | E-GEOD-13753 | biostudies-arrayexpress
Project description:Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues. Keywords: genetically modified tissue comparison
2009-06-08 | GSE13753 | GEO
Project description:Loss of Rb family in HSCs results in a severe phenotype, such as enhanced proliferation and increase in stem cell number. In addition, HSCs were higly mobilized but failed to transplant. Rb family deficient mice rapidly exhibit a myeloproliferative disease with eosinophilic characteristics. Meanwhile, the lymphoid compartment was severely decreased, due to high apoptotic activity in this lineage. Keywords: unpaired WT versus Rb family deficient KLS
2008-04-25 | GSE11253 | GEO
Project description:This serie was performed on liver progenitor isolated based on their expression of the Sca1 surface marker. It contains two independent samples from Rb family deficient liver and three independent samples from control liver, all isolated 2 weeks after Tamoxifen-induced Rb family ablation. Hematopoietic (CD45, Ter119) and endothelial (CD31) markers were used as negative selection markers to exclude blood or endothelial cells from the isolated fraction.
2015-11-15 | GSE63793 | GEO
Project description:The transcription factor E2F4 is a member of the E2F family of regulators which has critical roles in cell cycle control and differentiation. We investigated the genome-wide binding profile of E2F4 using a newly developed peak calling program based on a kernel density estimation and identified approximately 16 thousands E2F4 binding sites at a 1% FDR threshold, which potentially modulate 7,346 downstream target genes. Gene Ontology (GO) functional analysis of E2F4 target genes revealed several novel functions of E2F4 including I-kappaB kinase/NF-kappaB cascade, protein transport and targeting, protein folding, and sterol biosynthetic process. In addition to mRNA target genes, E2F4 also binds and regulates some miRNA targets such as let-7a, mir-17 and mir-22. Interestingly, we found that about 20% of E2F4 sites are in intergenic regions, which suggests that E2F4 may function at enhancer sites. De novo motif discovery revealed 5 novel, significantly enriched motifs within E2F4 sites. Only 5% of binding sites contain a canonical motif, indicating that E2F4 can use diverse motifs to bind DNA and regulate transcription. Overexpression of E2F4 and its cofactors such as RBL2 and DP-1, followed by microarray analysis, revealed that E2F4 functions as an activator and a repressor. Taken together, our genome-wide E2F4 ChIP sequencing data provided evidences of versatile physiological roles of E2F4 and insights into its functions. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2010-11-01 | E-GEOD-21489 | biostudies-arrayexpress
Project description:The retinoblastoma cell cycle regulator pRb and the two related proteins p107 and p130 are thought to suppress cancer development both by inhibiting the G1/S transition of the cell cycle in response to growth-arrest signals and by promoting cellular differentiation. Here, we investigated the phenotype of Rb family triple knock-out (TKO) embryonic stem cells as they differentiate in vivo and in culture. Confirming the central role of the Rb gene family in cell cycle progression, TKO mouse embryos did not survive past mid-gestation and differentiating TKO cells displayed increased proliferation and cell death. However, patterning and cell fate determination were largely unaffected in these TKO embryos. Furthermore, a number of TKO cells, including in the neural lineage, were able to exit the cell cycle in G1 and terminally differentiate. This ability of Rb family TKO cells to undergo cell cycle arrest was associated with the repression of target genes for the E2F6 transcription factor, uncovering a pRb-independent control of the G1/S transition of the cell cycle. These results show that the Rb gene family is required for proper embryonic development but is not absolutely essential to induce G1 arrest and differentiation in certain lineages.
2009-09-01 | GSE13408 | GEO
Project description:Loss of Rb family in HSC results in their sustained proliferation, impaired homeostasis and extramedullar mobility.
2017-05-24 | GSE98311 | GEO