Journal Article

Epigenome Microarray Platform for Proteome-Wide Dissection of Chromatin-Signaling Networks

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

2009

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino acids / Antibodies / Antibodies - analysis / Antigenic determinants / Biological effects / Biology / Cancer / Cell Biology/Cell Signaling / Chromatin / Chromatin - metabolism / Deoxyribonucleic acid / Dissection / DNA / DNA binding proteins / DNA damage / DNA methylation / DNA repair / Effectors / Epigenesis, Genetic / Epigenetic inheritance / Epigenetics / Epitopes / Genetics and Genomics/Epigenetics / Genome, Human / Hemp / Histones / Histones - metabolism / Humans / Identification / Immunodeficiency / Immunoglobulins / Knowledge management / Ligands / Molecular Biology/Chromatin Structure / Molecular Biology/Histone Modification / Molecular interactions / Mutation / Oncology / Peptides / Post-translation / Product information / Protein Array Analysis - methods / Protein Binding / Proteins / Proteome - analysis / Proteomes / Signal Transduction / Signaling / Surgery