Expression data from hESCs expressing RB7LP or T121
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29783 | GEO | 2012/06/29
SECONDARY ACCESSION(S): PRJNA141057
REPOSITORIES: GEO
Similar Datasets
Project description:We used microarray analysis to study the expression differences between controls and hESCs expressing RB7LP for 3 days, and controls and hESCs expressing T121 for 3 days. RB7LP is the large pocket fragment of the retinoblastoma protein (RB) fused to GFP, in which seven phosphorylation sites for Cdk have been mutated (Angus, SP et al. Mol Cell Biol 23, 8172 (Nov, 2003). T121 is a truncated form of the SV40 Large T (LT) viral oncoprotein that inactivates the function of the three members of the retinoblastoma (RB) protein family (RB, p107, p130). We plated hESCs that had been infected with inducible lentiviruses to express either RB7LP or T121. The day after plating, one well from each virus was treated with doxycyline to induce expression of either RB7LP or T121 and after 3 days were harvested for microrarray analysis.
2012-06-28 | E-GEOD-29783 | biostudies-arrayexpress
Project description:The epidermal-specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated Rb(F19/F19)K14cre;Rbl2-/- (pRb-;p130-) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb- and pRb-;p130- mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb-, pRb-;p107- and pRb-;p130- primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities. Keywords: skin, pRb, transgenic mice, p130
2007-11-13 | GSE9562 | GEO
Project description:The epidermal-specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated Rb(F19/F19)K14cre;Rbl2-/- (pRb-;p130-) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb- and pRb-;p130- mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb-, pRb-;p107- and pRb-;p130- primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities. Experiment Overall Design: Total RNA from pooled cells from each genotype were analyzed, per duplicate (pRb-/-;p107-/-, or pRb-/-;p130-/-) or triplicate (wild type, or pRb-/-), in mouse microarrays. Comparison was performed between the 4 different genotypes.
2008-06-16 | E-GEOD-9562 | biostudies-arrayexpress
Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Experiment Overall Design: Expression profiles of IMR90 cells before and after RNAi-mediated supppression of RB, p107 or p130 in growing, quiescent or ras-induced senescent conditions. RNA was extracted from growing, low serum (0.1% FBS), confluent, or ras-senescent cells.
2010-01-23 | E-GEOD-19864 | biostudies-arrayexpress
Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program.
2010-01-15 | GSE19864 | GEO
Project description:Adenovirus e1a induces quiescent human cells to divide. We found that e1a causes global relocalization of the RB-proteins (RB, p130, p107) and p300/CBP histone acetyltransferases on promoters that restricts H3K18ac to a limited set of genes to stimulate cell cycling and inhibit antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to cell cycle/growth genes, causing enrichment of p300/CBP, PCAF, H3K18ac, depletion of RB-proteins, and transcriptional activation. e1a also associates transiently with antiviral genes, causing enrichment for RB, p130, H4K16ac, increased nucleosome density, and repression. At later times, e1a and p107 bind mainly to development/differentiation genes, repressing transcription. The temporal order of e1a binding required its interactions with p300/CBP and RB-proteins. Our data uncover a defined transcriptional and epigenetic reprogramming leading to cellular transformation. Expression profiles and ChIP on chip genomewide experiments with dl1500 virus (expressing WT small e1a).
2008-08-26 | E-GEOD-12045 | biostudies-arrayexpress
Project description:Adenovirus e1a induces quiescent human cells to divide. We found that e1a causes global relocalization of the RB-proteins (RB, p130, p107) and p300/CBP histone acetyltransferases on promoters that restricts H3K18ac to a limited set of genes to stimulate cell cycling and inhibit antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to cell cycle/growth genes, causing enrichment of p300/CBP, PCAF, H3K18ac, depletion of RB-proteins, and transcriptional activation. e1a also associates transiently with antiviral genes, causing enrichment for RB, p130, H4K16ac, increased nucleosome density, and repression. At later times, e1a and p107 bind mainly to development/differentiation genes, repressing transcription. The temporal order of e1a binding required its interactions with p300/CBP and RB-proteins. Our data uncover a defined transcriptional and epigenetic reprogramming leading to cellular transformation. Expression profiles and ChIP on chip genomewide experiments with R2G mutant virus (expressing a mutated version of small e1a).
2008-08-26 | E-GEOD-12046 | biostudies-arrayexpress
Project description:The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence. Keywords: Gene expression analysis during cell cycle
2007-07-21 | GSE8537 | GEO
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis.
2014-01-01 | GSE37601 | GEO
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis.
2016-01-01 | GSE37576 | GEO