Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Interplay between c-Jun and TAp73M-NM-1/M-NM-2 contributes to the apoptosis-survival balance

ABSTRACT: The p53-family member p73 functions in various cellular signaling pathways and can have tumor suppressor properties. Several isoforms of p73 exist that differ considerably in their function. Whereas the functions of the N-terminal isoforms (TA and M-NM-^TNp73) and their opposing pro- and anti-apoptotic roles became evident, the functional differences of the distinct C-terminal spliceforms of TAp73 have remained unclear. Here, we characterized the genomic binding sites for TAp73M-NM-1 and TAp73M-NM-2 and identified a specific p73 consensus binding-motif. Furthermore, an AP1 motif is strongly enriched close to binding sites for TAp73M-NM-1. These AP1 motif-containing target genes are selectively upregulated by TAp73M-NM-1, while their mRNA expression is repressed upon TAp73M-NM-2 induction. Recruitment of c-Jun to the respective AP1 sites was impaired upon TAp73M-NM-2 expression in part due to downregulation of c-Jun. We show that several of these AP1-site containing TAp73M-NM-1-induced genes reduce on apoptosis-induction suggesting an underlying molecular mechanism for the observed functional differences between TAp73M-NM-1 and TAp73M-NM-2. ChIP-seq and RNA-seq profiles of TAp73alpha, TAp73beta and p53 stably transfected in human osteosarcoma Saos cells

ORGANISM(S): Homo sapiens

SUBMITTER: Marion Lohrum

PROVIDER: E-GEOD-15780 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis-survival balance.

Koeppel Max M van Heeringen Simon J SJ Kramer Daniela D Smeenk Leonie L Janssen-Megens Eva E Hartmann Marianne M Stunnenberg Hendrik G HG Lohrum Marion M

Nucleic acids research 20110331 14

The p53-family member p73 plays a role in various cellular signaling pathways during development and growth control and it can have tumor suppressor properties. Several isoforms of p73 exist with considerable differences in their function. Whereas the functions of the N-terminal isoforms (TA and ΔNp73) and their opposing pro- and antiapoptotic roles have become evident, the functional differences of the distinct C-terminal splice forms of TAp73 have remained unclear. Here, we characterized the g ...[more]

PMID: 21459846

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Project description:Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here we present sequential ChIP-bisulfite-sequencing (ChIP- BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin- immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 tri- methylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in Dnmt triple- knock-out (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at megabase scale. Our strategy provides an unique way of investigating global interdependencies between DNA methylation and other chromatin features. ChIP (chromatin immunoprecipitation) is followed by bisulfite conversion and deep sequencing to directly assess DNA methylation levels in captured chromatin fragments (ChIP-BS-seq). We used ChIP-BS-seq to study the potential global cross-talk between H3K27me3 and DNA methylation, which are both linked to repression. First, we used capturing of methylated DNA, followed by bisulfite-deep sequencing (MethylCap-BS-seq). Genomic DNA isolated from normal and tumor colon tissues was used for MethylCap-BS-seq as well as for conventional MethylCap-seq experiments. Second, we performed ChIP-BS-seq on H3K27me3, using HCT116 colon carcinoma cells. Third, to further study the relevance of the observations, we generated genome-wide profiles for H3K27me3 and DNA methylation by conventional ChIP-seq and MethylCap-seq, and RNA-seq, respectively. Finally, we performed H3K27me3-ChIP-BS-seq and MethylCap-seq on wild-type mouse ES cells as well as Dnmt-triple-knockout (TKO) mouse ES cells.

Dataset Information

Interplay between c-Jun and TAp73M-NM-1/M-NM-2 contributes to the apoptosis-survival balance

Publications

Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis-survival balance.

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