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Quantitative analysis of proliferative and Ras-induced senescent human primary fibroblasts transcriptomes

ABSTRACT: The goals of this study is to analyse transcriptionnal changes in senescent cells and to compare them with ChIPseq data for several histones marks and proteins of the SUMO machinery mRNA profiling of proliferative versus Ras-induced senescent humain primary fibroblasts 5 days post-infection

ORGANISM(S): Homo sapiens

SUBMITTER: Tao YE

PROVIDER: E-GEOD-42212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.

Neyret-Kahn Hélène H Benhamed Moussa M Ye Tao T Le Gras Stéphanie S Cossec Jack-Christophe JC Lapaquette Pierre P Bischof Oliver O Ouspenskaia Maia M Dasso Mary M Seeler Jacob J Davidson Irwin I Dejean Anne A

Genome research 20130726 10

Despite numerous studies on specific sumoylated transcriptional regulators, the global role of SUMO on chromatin in relation to transcription regulation remains largely unknown. Here, we determined the genome-wide localization of SUMO1 and SUMO2/3, as well as of UBC9 (encoded by UBE2I) and PIASY (encoded by PIAS4), two markers for active sumoylation, along with Pol II and histone marks in proliferating versus senescent human fibroblasts together with gene expression profiling. We found that, whe ...[more]

PMID: 23893515

Similar Datasets

Genome wide occupancy of SUMO machinery in proliferative and Ras-induced senescent human primary fibroblasts

Project description:Transcription factors represent one of the largest groups of proteins regulated by SUMO, and their modification has generally been correlated with transcriptional repression. However, as most of the studies focus on specific sumoylated transcriptional regulators, the distribution and global role of SUMO on chromatin in relation to transcription regulation remain largely unknown. To investigate this role, we determined the occupancy of SUMO machinery proteins on chromatin by ChIP coupled to sequencing in human primary cells. Examination of 3 histone modifications, Polymerase II, SUMO1, SUMO2, Ubc9 and PIASy in proliferative and Ras-induced senescent fibroblasts.

2013-07-24 | E-GEOD-42211 | biostudies-arrayexpress

SUMO is an Integral and Instructive Component of Chromatin in Cell Growth and Senescence

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-24 | E-GEOD-42213 | biostudies-arrayexpress

Sumoylation at Chromatin Governs Coordinated Repression of a Transcriptionnal Program Essential for Cell Growth and Proliferation 2

Project description:mRNA profiling of proliferative versus Ras-induced senescent human primary fibroblasts 5 days post-infection. The goals of this study is to analyse transcriptional changes in senescent cells (RASv12 infected cells)

2013-11-25 | E-MEXP-3777 | biostudies-arrayexpress

Gene expression changes associated with 3D growth of TAF4 knock out fibroblasts

Project description:Collagen 6A3 (Col6a3), a component of extracellular matrix, is often up-regulated in tumours and is believed to play a pro-oncogenic role. However the mechanisms of its tumorigenic activity are poorly understood. We show here that Col6a3 is highly expressed in densely growing mouse embryonic fibroblasts (MEFs). In MEFs where the TAF4 subunit of general transcription factor IID (TFIID) has been inactivated, elevated Col6a3 expression prevents contact inhibition promoting their 3 dimensional growth as foci and fibrospheres. Analyses of gene expression in densely growing Taf4-/- MEFs revealed repression of the Hippo pathway and activation of Wnt signalling. The Hippo activator Kibra/Wwc1 is repressed under dense conditions in Taf4-/- MEFs, leading to nuclear accumulation of the proliferation factor YAP1 in the cells forming 3D foci. At the same time, Wnt9a is activated and the Sfrp2 antagonist of Wnt signalling is repressed. Surprisingly, treatment of Taf4-/- MEFs with all-trans retinoic acid (ATRA) restores contact inhibition suppressing 3D growth. ATRA represses Col6a3 expression independently of TAF4 expression and Col6a3 silencing is sufficient to restore contact inhibition in Taf4-/- MEFs and to suppress 3D growth by reactivating Kibra expression to induce Hippo signalling and by inducing Sfrp2 expression to antagonize Wnt signalling. All together, these results reveal a critical role for Col6a3 in regulating both Hippo and Wnt signalling to promote 3D growth, and show that the TFIID subunit TAF4 is essential to restrain the growth promoting properties of Col6a3. Our data provide new insight into the role of extra cellular matrix components in regulating cell growth. 6 samples corresponding to non-confluent cells, confluent cells and cells growing as fibrospheres were analyzed. Each growing condition was done in duplicate.

2014-03-06 | E-GEOD-53098 | biostudies-arrayexpress

VL30 retro-transposons are TRIM24-repressed enhancers that generate non-coding RNA to regulate gene expression in mouse hepatocytes.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-01 | E-GEOD-39853 | biostudies-arrayexpress

Transcriptome-profiling (RNA-seq) and Ribosome-profiling (Ribo-seq) in proliferation, quiescence, senescence and transformed states.

Project description:We applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells under the following conditions: normal proliferation, quiescence (induced by serum depletion), senescence (induced by activation of the oncogenic RASG12V gene, and examined at early (5 days; pre-senescent state) and late (14 days; fully senescent state) time points), and neoplastic transformation (induced by RASG12V in the background of stable p53 and p16INK4A knockdowns and SV40 small-T expression. RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed. Ribosome profiling, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed.

2013-03-24 | E-GEOD-42509 | biostudies-arrayexpress

H3K9me3 ChIPseq experiments from PD IMR90s

Project description:H3K9me3 ChIPseq in Proliferating and Senescent IMR90s We used ChIP-seq to examine the global binding of H3K9me3 in human IMR90 replicative senescence (RS) and oncogene-induced (OIS)

2014-12-15 | E-GEOD-53329 | biostudies-arrayexpress

A Genome-wide Chronological Study of Gene Expression and Two Histone Modifications, H3K4me3 and H3K9ac, during Developmental Leaf Senescence [RNA-seq]

Project description:The genome-wide abundance of two histone modifications, H3K4me3 and H3K9ac, both associated with actively expressed genes, was monitored in Arabidopsis thaliana leaves at different time points during developmental senescence, along with expression in the form of RNA-seq data. H3K9ac and H3K4me3 marks were highly convergent at all stages of leaf aging, but H3K4me3 marks covered nearly twice the gene area as H3K9ac marks. Genes with the greatest fold-change in expression displayed the largest positively-correlated percent change in coverage for both marks. Most senescence up-regulated genes were pre-marked by H3K4me3 and H3K9ac, but at levels below the whole-genome average, and for these genes, gene expression increased without a significant increase in either histone mark. However, for a subset of genes showing increased or decreased expression, the respective gain or loss of H3K4me3 marks were found to closely match the temporal changes in mRNA abundance. 22% of genes that increased expression during senescence showed accompanying changes in H3K4me3 modification, and they include numerous regulatory genes, which may act as primary response genes. RNA-seq data at different stages of leaf aging.

2015-04-11 | E-GEOD-67777 | biostudies-arrayexpress

Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

Project description:We have found that thyroid hormones (THs), acting as soluble integrin αvβ3 ligands, activate growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated αvβ3 integrin signaling promotes TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF. CUTLL1 cells were treated with T3- and T4-bound agarose or agarose alone for 24hrs. Total RNA was harvested from cells and used for expression profiling via RNA-seq.

2015-02-18 | E-GEOD-63122 | biostudies-arrayexpress

The yeast osmostress response is carbon source dependent

Project description:Adaptation to altered osmotic conditions is a fundamental property of living cells and has been studied in particular detail in the yeast Saccharomyces cerevisiae. Yeast cells accumulate glycerol as compatible solute, controlled at different levels by the High Osmolarity Glycerol (HOG) response pathway. Up to now, essentially all osmostress studies in yeast have been performed with glucose as carbon and energy source, which is metabolised by glycolysis with glycerol is as a normal by-product. Here we investigated the response of yeast to osmotic stress when yeast is respiring ethanol as carbon and energy source. Remarkably, yeast cells do not accumulate glycerol under these conditions and it appears that trehalose may partly take over the role as compatible solute. The HOG pathway is activated in very much the same way as in during growth on glucose medium and is also required for osmotic adaptation. Slower volume recovery was observed in ethanol-grown cells as compared to glucose-grown cells. Dependence on key regulators as well as the global gene expression profile were similar in many ways to those previously observed in glucose-grown cells. However, there are indications that cells re-arrange redox-metabolism when respiration is hampered under osmostress, a feature that could not be observed in glucose-grown cells.

2017-02-27 | E-MTAB-5313 | biostudies-arrayexpress

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