Expanding the landscape of chromatin modification (CM)-related functional domains and genes in human.

TitleExpanding the landscape of chromatin modification (CM)-related functional domains and genes in human.
Publication TypeJournal Article
Year of Publication2010
AuthorsPu, S., Turinsky A. L., Vlasblom J., On T., Xiong X., Emili A., Zhang Z., Greenblatt J., Parkinson J., and Wodak S. J.
JournalPLoS One
Volume5
Issue11
Paginatione14122
Date Published2010
ISSN1932-6203
KeywordsAnimals, Binding Sites, Caenorhabditis elegans Proteins, Chromatin, Computational Biology, Databases, Genetic, DNA Methylation, Drosophila Proteins, Gene Expression Profiling, Histones, Humans, Methylation, Mice, Protein Processing, Post-Translational, Proteins, Saccharomyces cerevisiae Proteins
Abstract

Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins) in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

DOI10.1371/journal.pone.0014122
Alternate JournalPLoS ONE
PubMed ID21124763
PubMed Central IDPMC2993927
Grant List82940 / / Canadian Institutes of Health Research / Canada