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E2f regulation of gene expression in the liver [12 mo]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE71381 | GEO | 2016/07/01

SECONDARY ACCESSION(S): PRJNA291071

REPOSITORIES: GEO

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E2f regulation of gene expression in the liver [12 mo]

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

E2f regulation of gene expression in the liver [1 mo]

Project description:E2Fs 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.

2016-07-01 | GSE71380 | GEO

E2f regulation of gene expression in the liver [1 mo]

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

Identification of E2F targets in MEFs

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

Identification of E2F targets in MEFs

Project description:ChIP sequencing for E2F1, E2F3A and E2F3B in mouse embryonic fibroblasts

2016-07-01 | GSE71376 | GEO

Transcriptomes of E2F7/8 DKO liver tumors

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

E2F3a mediates cocaine action in nucleus accumbens via alternative splicing and transcription

Project description:Long-lasting changes in neuronal gene expression in brain reward regions, including the nucleus accumbens (NAc), contribute to the persistent functional changes in the addicted brain. Our group and others have demonstrated that altered expression or activity of several candidate transcription factors in NAc regulates drug responses. In a recent study from our group (Feng et al., 2014), involving large-scale genome-wide datasets, E2F3 was predicted as a prominent upstream regulator of cocaine-induced changes in gene expression and alternative splicing. Here, we show that E2F3a, but not E2F3b, expression in NAc regulates cocaine-induced locomotor and reward behavior. Furthermore, we demonstrate that E2F3a overexpression recapitulates a considerable portion of genome-wide transcriptional profiles and alternative splicing induced by cocaine administration. We further validate functional binding of E2F3a at several target genes following cocaine exposure. These novel findings support a crucial role for E2F3a in the regulation of cocaine-elicited behavioral states and molecular mechanisms.

2017-08-23 | GSE85936 | GEO

Deregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor development

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

ATAC-seq for SK-HEP-1 cell line with or without sirolimus treatment

Project description:The openness of chromatin affects the expression and regulation of genes. In order to figure out the changes of transcriptional factors after sirolimus treatment in hepatocellular carcinoma, ATAC-seq was performed for human hepatocellular carcinoma cell line SK-HEP-1. Here, we found that a series of transcriptional factors, including E2F1, SP1, M2F1, etc. enhanced binding to DNA after sirolimus treatment.

2023-12-06 | GSE239926 | GEO

Expression data from control, E2f TKO, Myc KO and E2f/Myc QKO crypts

Project description:Combined ablation of Myc and E2f1-3 results in disruption of crypt-villus integrity in the small intestine due to a S-G2 cell cycle blockade. We used Affymetrix microarrays to profile the global gene expression changes caused by loss of Myc and/or E2f1-3.

2015-07-20 | GSE56006 | GEO

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