UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

6-1-2011

Document Type

Article

Medical Subject Headings

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

Disciplines

Biochemistry | Enzymes and Coenzymes | Genetics and Genomics | Medicinal-Pharmaceutical Chemistry | Therapeutics

Abstract

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.

Rights and Permissions

Citation: PLoS Genet. 2011 Jun;7(6):e1002112. doi: 10.1371/journal.pgen.1002112. Epub 2011 Jun 2. Link to article on publisher's site

Comments

Copyright: © 2011 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.