Epigenome microarray platform for proteome-wide dissection of chromatin-signaling networks

Dennis J. Bua, Alex J. Kuo, Peggie Cheung, Chih Long Liu, Valentina Migliori, Alexsandra Espejo, Fabio Casadio, Christian Bassi, Bruno Amati, Mark T. Bedford, Ernesto Guccione, Or Gozani

Research output: Contribution to journalArticlepeer-review

Abstract

Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin.

Original languageEnglish
Article numbere6789
JournalPLoS One
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 26 2009

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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