The Histone Code of Toxoplasma gondii Comprises Conserved and Unique Post- translational Modifications

NARDELLI S; CHE FY; SILMON DE MONERRI NC; XIAO H; NIEVES E; MADRID-ALISTE C; ANGEL SO; SULLIVAN WJ; ANGELETTI R; KIM K; WEISS LM

Mbio

American Society for Microbiolgy

Año: 2013

2150-7511

Epigenetic gene regulation has emerged as a major mechanism for gene regulation in all eukaryotes. Histones are small, basic proteins that constitute the major protein component of chromatin, and post-translational modifications (PTM) of histones are essential for epigenetic gene regulation. The different combinations of histone PTM form the histone code for an organism, marking functional units of chromatin that recruit macromolecular complexes that govern chromatin structure and regulate gene expression.To characterize the repertoire of T. gondii histone PTM, we enriched histones using standard acid-extraction protocols and analyzed them with several complementary middle-down and bottom-up proteomic approaches with the high-resolution Orbitrap mass spectrometer using collision-induced dissociation (CID), higher-energy collisional dissociation (HCD) and/or electron-transfer dissociation (ETD) fragmentation. We identified 249 peptides with unique combinations of PTM that comprise the T. gondii histone code. T. gondii histones share a high degree of sequence conservation with human histones, and many modifications are conserved between both species. In addition, T. gondii histones have unique modifications not previously identified in other species. Finally, T. gondii histones are modified by succinylation, propionylation and formylation, recently described histone PTM that have not previously been identified in  parasitic protozoa. The characterization of the T. gondii histone code will facilitate in depth analysis of how epigenetic regulation affects gene expression in pathogenic apicomplexan parasites and identifies a new model system for elucidating the biological function of novel histone PTM.