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Unknown,Transcriptomics,Genomics,Proteomics

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TAF6 orchestrates transcription programs and apoptosis in the absence of p53

ABSTRACT: The decision of metazoan cells to live or undergo programmed cell death hinges on the balance between the levels of pro- versus anti-apoptotic gene products. The general RNA polymerase II (Pol II) transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 is a co-activator for the pro-apoptotic p53 tumour suppressor protein. Our previous studies identified a specialized isoform of TAF6, termed TAF6 that can specifically be induced in apoptosis. To elucidate the impact of TAF6 on gene expression and cell death, we employed modified antisense oligonucleotides to enforce expression of endogenous TAF6. The induction of endogenous TAF6 triggered apoptosis in several cancer cell lines. Importantly, TAF6 also induces apoptosis in tumor cell lines devoid of p53, placing TAF6 function downstream of p53. Microarray experiments uncovered a TAF6-induced transcriptome landscape displaying enhanced expression of genes of the Notch, oxidative stress, integrin, p53 and apoptosis pathways. Our data show that the TAF6 pathway is a pivotal signalling nexus that controls pro-apoptotic gene expression programs. Keywords: Treatment with splice site switching antisense oligonucleotides, induction of apoptosis Biological triplicates, 3 conditions: control oligonucleotide, Taf6 oligonucleotide, specificity control Bcl-x oligonucleotide

ORGANISM(S): Homo sapiens

SUBMITTER: Arndt Benecke

PROVIDER: E-GEOD-8752 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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p53 independent TAF6delta target genes.

Project description:To elucidate the impact of TAF6d on cell death and gene expression, here we have employed modified antisense oligonucleotides to enforce expression of endogenous TAF6d. The induction of endogenous TAF6d triggered apoptosis in tumor cell lines, including cells devoid of p53. Microarray experiments revealed that TAF6d activates gene expression independently of cellular p53 status. Our data define TAF6d as a pivotal node in a signaling pathway that acts immediately downstream of p53 to control gene expression programmes and apoptosis. Keywords: Treatment with splice site switching antisense oligonucleotides, induction of apoptosis Biological triplicates, 4 conditions: isogenic p53+/+ and -/- cells; control oligonucleotide, TAF6 AS2 oligonucleotide

2008-06-26 | E-GEOD-10795 | biostudies-arrayexpress

Determining the impact of alternative splicing events on transcriptome dynamics

Project description:Background The complete sequencing of the human genome and its subsequent analysis revealed a predominant role for alternative splicing in the generation of proteome diversity. Splice switching oligonucleotides (SSOs) are a powerful and specific tool to experimentally control alternative splicing of endogenous messenger RNAs in living cells. SSOs also have therapeutic potential to treat diseases that are caused by aberrant splicing. The assignment of biological roles to alternative splicing events of currently unknown function promises to provide a largely untapped source of potential new therapeutic targets. Here we have developed a protocol that combines high sensitivity microarrays with the transfection of SSOs to monitor global changes in gene expression downstream of alternate, endogenous splice events. Findings When applied to a well-characterized splicing event in the Bcl-x gene, the application of high sensitivity microarrays revealed a link between the induction of the Bcl-xS isoform and the repression of genes involved in protein synthesis. Conclusions The strategy introduced herein provides a useful approach to define the biological impact of any given alternative splicing event on global gene expression patterns. Furthermore, our data provide the first link between Bcl-xS expression and the repression of ribosomal protein gene expression. Biological triplicates, 2 conditions: control oligonucleotide, Bcl-x oligonucleotide

2008-10-02 | E-GEOD-9851 | biostudies-arrayexpress

EBER2 RNA-induced transcriptome changes identify cellular processes likely targeted during Epstein Barr Virus infection.

Project description:Little is known about the physiological role of the EBER1 and 2 nuclear RNAs during Epstein Barr viral infection. The cellular transcription response to EBER2 expression using the wild-type and an internal deletion mutant was determined. Significant changes in gene expression patterns were observed. A functional meta-analysis of the regulated genes points to inhibition of stress and immune responses, as well as activation of cellular growth and cytoskeletal reorganization as potential targets for EBER2 RNA. Different functions can be assigned to different parts of the RNA. These results provide new avenues to the understanding of EBER2 and EBV biology. Keywords: Overexpression of non-translated RNA Biological relicates, 3 conditions: empty expression vector (pUC-18), pUC-18-EBER2, pUC-18-EBER2-L2

2008-10-02 | E-GEOD-11093 | biostudies-arrayexpress

Modulation of gene expression in U251 glioblastoma cells by binding of mutant p53 to intronic and intergenic sequences

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2010-06-24 | E-GEOD-13991 | biostudies-arrayexpress

Gene expression profiling of human anaplastic thyroid carcinoma cells by microarray

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2010-06-25 | E-GEOD-12912 | biostudies-arrayexpress

Gene expression profile in pelvic organ prolapse

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2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress

Transcription profiling of human cell types after 24 hrs serum starvation

Project description:Comparison of cell types after 24 hrs serum starvation.

2006-05-01 | E-MEXP-519 | biostudies-arrayexpress

Differential Gene Expression Between Brown Norway and Sprague Dawley Rats in Response to Renal Ischemia Reperfusion

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2007-12-27 | E-GEOD-9943 | biostudies-arrayexpress

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2008-05-22 | E-GEOD-9796 | biostudies-arrayexpress

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