E2f regulation of gene expression in the liver [1 mo]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71380 | GEO | 2016/07/01
SECONDARY ACCESSION(S): PRJNA291067
REPOSITORIES: GEO
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Project description:E2F’s are regulators of the cell cycle and are involved in development and hepatocellular carcinoma. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008. Microarrays were used to evaluate transcriptional changes in spontaneous hepatocellular carcinoma that arose due to alterations in E2F expression.
2016-07-01 | GSE71381 | GEO
Project description:E2FÂs are regulators of the cell cycle and are involved in development. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008. Microarrays were used to evaluate transcriptional changes due to alterations in E2F expression during liver development. Affymetrix microarrays were performed using RNA samples from 4 weeks (1 month) old livers from wildtype (wt), E2F3a knockout (3aKO) E2f1 knock-in (1KI) and E2f3b knock-in (3bKI) mice.
2016-07-01 | E-GEOD-71380 | biostudies-arrayexpress
Project description:E2Fâs are regulators of the cell cycle and are involved in development and hepatocellular carcinoma. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008. Microarrays were used to evaluate transcriptional changes in spontaneous hepatocellular carcinoma that arose due to alterations in E2F expression. Affymetrix microarrays were performed using mRNA samples from 12 month old livers from wildtype (wt), E2F3a knockout (3aKO) E2f1 knock-in (1KI) and E2f3b knock-in (3bKI) mice. Wt and 3aKO samples were from normal liver and 1KI and 3bKI samples were from spontaneously occurring hepatocellular carcinoma.
2016-07-01 | E-GEOD-71381 | biostudies-arrayexpress
Project description:ChIP sequencing for E2F1, E2F3A and E2F3B in mouse embryonic fibroblasts E2F1, E2F3A and E2F3B ChIPs were performed in mouse embryonic fibroblasts stably overexpressing the proteins. ChIP DNA was processed to generate libraries and then sequenced using the Illumina platform.
2016-07-01 | E-GEOD-71376 | biostudies-arrayexpress
Project description:ChIP sequencing for E2F1, E2F3A and E2F3B in mouse embryonic fibroblasts
2016-07-01 | GSE71376 | GEO
Project description:E2F transcriptional activators and repressors regulate cell cycle-dependent gene expression. Using a series of E2f loss- and gain-of-function mice we show that development is relatively insensitive to alterations in individual E2F levels and composition. However, modest increases in E2F transcriptional output (E2f7Δ/Δ;E2f8Δ/Δ, E2f1KI/1KI and E2f3bKI/3bKI) resulted in spontaneous hepatocellular carcinoma (HCC) without additional organ involvement, whereas decreases (E2f1-/- and E2f3b-/-) protected against HCC. DNA binding domain-, cell type- and temporal-specific gene ablation strategies defined a cell autonomous oncogenic role for E2F1/3B and a tumor suppressor role for E2F8 in hepatocytes during early post-natal liver development. Chromatin binding and expression profiling revealed a mechanism involving activation by E2F1/3B and repression by E2F7/8 to antagonistically regulate a common set of target genes associated with HCC progression. Thus, while development is sufficiently robust to withstand changes in E2F composition and activity, the liver is uniquely sensitive to perturbations in E2Fs. In summary, precise E2F transcriptional output in hepatocytes during early adolescence is critical to foster a cancer-free life span.
2016-10-18 | GSE71574 | GEO
Project description:E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided in two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer. We have previously reported that combined Rb1-Rbl1 and Rb1-E2F1 ablation in epidermis produces important alterations in epidermal proliferation and differentiation, leading to tumor development. However, the possible roles of E2F4 in this context are still to be determined. Here we show the absence of any discernible phenotype in the skin of mice lacking of E2F4. In contrast, the inducible loss of Rb1 in the epidermis of E2F4-null mice produced multiple skin abnormalities including altered differentiation and proliferation, spontaneous wounds, carcinoma in situ development and stem cell perturbations. All these phenotypic alterations are associated with extensive gene expression changes, the induction of c-myc and the Akt activation. Moreover, the whole transcriptome analyses in comparison with previous models generated also revealed extensive changes in multiple repressive complexes and in transcription factor activity. These results point to E2F4 as a master regulator in multiple steps of epidermal homeostasis in Rb1 absence.
2016-07-09 | GSE84206 | GEO
Project description:We demonstrate that the cell cycle regulators, E2f /Dp and Rb, control the transcription of ribosomal proteins (RP) in Drosophila embryos. Mutation of E2f1 or Dp and over expression of Rbf1 increase and reduce RP transcription, respectively. Although E2f/Dp/Rb might exert this effect through a repressor complex, the regulatory regions of RP genes do not show an enrichment of canonical E2f binding sites. In addition, E2f1, Dp and Rbf1 also regulate the expression of RACK1, a ribosomal component and a negative regulator of cell cycle progression. These findings strengthen the coupling of cell cycle regulation to protein biosynthesis. Keywords: genotype response
2008-04-27 | GSE7655 | GEO
Project description:We demonstrate that the cell cycle regulators, E2f /Dp and Rb, control the transcription of ribosomal proteins (RP) in Drosophila embryos. Mutation of E2f1 or Dp and over expression of Rbf1 increase and reduce RP transcription, respectively. Although E2f/Dp/Rb might exert this effect through a repressor complex, the regulatory regions of RP genes do not show an enrichment of canonical E2f binding sites. In addition, E2f1, Dp and Rbf1 also regulate the expression of RACK1, a ribosomal component and a negative regulator of cell cycle progression. These findings strengthen the coupling of cell cycle regulation to protein biosynthesis. Experiment Overall Design: Our study examines the genomic response of intact Drosophila embryos to the genetic manipulation of E2F/Rb pathway molecules. For over-expression experiments, Arm-Gal4 stocks were crossed to UAS-gene stocks for the following genes: E2f1/Dp, E2f2/Dp, Rbf1, and E2f1336-805 (a dominant negative form of E2f1 lacking the DNA binding domain) [16]. The E2f17172 and E2f191 null alleles were balanced by TM3[Kr-GFP]. Dpa2 and Dpa4 null alleles were balanced by CyO[Kr-GFP]. 14-16 hr E2f17172/E2f191 null mutant embryos were hand selected based on the absence of fluorescent Bolwigâs organs in Kr-GFP balanced stocks using a Zeiss stereomicroscope equipped with epifluorescence. E2f17172/E2f191 and Dpa2/Dpa4 null mutant embryos (8-10h) were selected using the COPASTM SELECT system for automated sorting of multi-cellular organisms. Eighteen RNA samples, two from each cross, were obtained from approximately 200 to 700 embryos per sample. For each cross, 2 h embryo collections were aged for 8 to 14 h at 25oC, quick frozen in an ethanol/dry ice mixture, and stored at -80 oC. The RNA was prepared for microarray analysis in accordance with Affymetrix instructions.
2008-06-15 | E-GEOD-7655 | biostudies-arrayexpress
Project description:To identify genes specifically activated by deregulated E2F, we examined gene expression profiles using human normal fibroblasts (HFFs), which were starved of serum and re-stimulated with serum, over-expressed with E2F1 or expressed with adenovirus E1a to forcedly inactivate RB. To identify genes activated by growth stimulation, human normal fibroblasts (HFFs) were starved of serum for 48 hr, infected with control virus, restimulated with serum or left serum-starved for 18 hr and harvested. To identify genes actived by deregulated E2F, HFFs were starved of serum for 48 hr, infected with control virus, adenovirus expressing E2F1 or adenovirus E1a, further cultured in the absence of serum for 18 hr and harvested. Gene expression profiles of ecach sample were examined by DNA microarray.
2015-11-20 | E-GEOD-67887 | biostudies-arrayexpress