Genomics

Dataset Information

153

Genome-wide analysis of tumor suppressive programs during p53-induced regression of Myc-driven lymphomas [ChIP-Seq]


ABSTRACT: The tumor suppressor p53 is a transcription factor that controls the response to stress. Here, we dissected the transcriptional programs triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. p53 recruitment at these sites was mainly mediated through protein-protein or protein-chromatin interactions and, only for a small fraction, through recognition of the 20 base-pair p53 consensus motif. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. p53 also targeted unmarked distal sites devoid of activation marks, at which binding was prevalently driven by recognition of the consensus motif. At all sites, our data highlighted a functional role for the canonical, unsplit consensus element, but did not provide evidence for p53 recruitment by split motifs. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 re-activation and tumor regression. Overall design: Mapping p53 binding sites in Eµ-myc lymphomas following p53 restoration.

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Marco J. Morelli  

PROVIDER: GSE80186 | GEO | 2017-02-14

SECONDARY ACCESSION(S): PRJNA318259

REPOSITORIES: GEO

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Publications

Genome-wide analysis of p53-regulated transcription in Myc-driven lymphomas.

Tonelli C C   Morelli M J MJ   Sabò A A   Verrecchia A A   Rotta L L   Capra T T   Bianchi S S   Campaner S S   Amati B B  

Oncogene 20170116 21


The tumour suppressor p53 is a transcription factor that controls cellular stress responses. Here, we dissected the transcriptional programmes triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. Only a small fraction of these sites showed the 20 base-pair p53 consensus motif, suggesti  ...[more]

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