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Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells.

PLoS genetics | Jun 9, 2011

Peptidylarginine deiminase IV (PADI4) catalyzes the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline, and this activity has been linked to the repression of a limited number of target genes. To broaden our knowledge of the regulatory potential of PADI4, we utilized chromatin immunoprecipitation coupled with promoter tiling array (ChIP-chip) analysis to more comprehensively investigate the range of PADI4 target genes across the genome in MCF-7 breast cancer cells. Results showed that PADI4 is enriched in gene promoter regions near transcription start sites (TSSs); and, surprisingly, this pattern of binding is primarily associated with actively transcribed genes. Computational analysis found potential binding sites for Elk-1, a member of the ETS oncogene family, to be highly enriched around PADI4 binding sites; and coimmunoprecipitation analysis then confirmed that Elk-1 physically associates with PADI4. To better understand how PADI4 may facilitate gene transactivation, we then show that PADI4 interacts with Elk-1 at the c-Fos promoter and that, following Epidermal Growth Factor (EGF) stimulation, PADI4 catalytic activity facilitates Elk-1 phosphorylation, histone H4 acetylation, and c-Fos transcriptional activation. These results define a novel role for PADI4 as a transcription factor co-activator.

Pubmed ID: 21655091 RIS Download

Mesh terms: Binding Sites | Breast Neoplasms | Cell Line, Tumor | Female | Genome, Human | Genome-Wide Association Study | Humans | Hydrolases | Phosphorylation | Promoter Regions, Genetic | Proto-Oncogene Proteins c-fos | Transcriptional Activation | ets-Domain Protein Elk-1

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK069710
  • Agency: NIDDK NIH HHS, Id: R01 DK058110
  • Agency: NIDDK NIH HHS, Id: DK58110
  • Agency: NIDDK NIH HHS, Id: R56 DK069710
  • Agency: NIDDK NIH HHS, Id: R01 DK069710

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UCSC Genome Browser

A collection of genomes which include reference sequences and working draft assemblies, as well as a variety of tools to explore these sequences. The Genome Browser zooms and scrolls over chromosomes, showing the work of annotators worldwide. The Gene Sorter shows expression, homology and other information on groups of genes that can be related in many ways. Blat quickly maps your sequence to the genome. The Table Browser provides access to the underlying database. VisiGene lets you browse through a large collection of in situ mouse and frog images to examine expression patterns. Genome Graphs allows you to upload and display genome-wide data sets. Also provided is a portal to the Encyclopedia of DNA Elements (ENCODE) and Neandertal projects.

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Gene Expression Omnibus

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