Transcriptomics

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Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.


ABSTRACT: Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and SULF2, which encodes an extracellular heparan sulfate 6-O-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression, and similar to silencing of TP53, RNA interference-mediated suppression of SULF2 results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology. Expression profiling experiments were performed to perturb the p53 status in cancer cell lines as a means of identifying novel members of the p53 pathway.

ORGANISM(S): Homo sapiens  

SUBMITTER: Robert L Diaz  Peter S Linsley  Michele Cleary  Nelson Chau  Paul Warrener  Jeffrey Bradshaw  Aaron Chang  Matthew A Saunders  Michele A Cleary  Chun Cheng 

PROVIDER: E-GEOD-15440 | ArrayExpress | 2010-06-20

SECONDARY ACCESSION(S): GSE15440PRJNA115801

REPOSITORIES: GEO, ArrayExpress

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Publications

Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.

Chau B Nelson BN   Diaz Robert L RL   Saunders Matthew A MA   Cheng Chun C   Chang Aaron N AN   Warrener Paul P   Bradshaw Jeffrey J   Linsley Peter S PS   Cleary Michele A MA  

Cancer research 20090203 4


Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with  ...[more]

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