title: Exploration of mechanisms in nutriepigenomics: Identification of chromatin-modifying compounds from Olea Europaea.
abstract: Chemical modification of histones represents an important epigenetic mechanism critical for DNA metabolism including, transcription, replication and repair. A well-known example is maintenance of histone acetylation status by the opposing actions of histone acetyltransferase and histone deacetylase enzymes which add and remove acetyl groups on lysine residues on histone tails, respectively. Similarly, histone methyltransferase and histone demethylase enzymes are responsible for adding and removing methyl groups on histone tails, respectively. Further, there is accumulated evidence indicating a histone code where combinations of different chemical modifications on histone tails act in concert to regulate DNA metabolic events. Although numerous compounds have been developed to specifically alter the function of chromatin modifying enzymes (for example, histone deacetylase inhibitors are relatively well-investigated), we are only at the early stages of understanding the epigenetic effects of dietary compounds. Here we used in silico molecular modeling approaches combined with known experimental affinities for controls, to identify potential chromatin modifying compounds derived from Olea Europaea. Our findings indicate that various compounds derived from Olea Europaea have the ability to bind to the active site of different chromatin modifying enzymes, with an affinity analogous or higher than that for a known positive control. Further, we initiated the process of validating targets using in vitro binding and enzyme activity inhibition assays and provide initial findings of potential epigenetic effects in a clinical context. Overall, our findings can be considered as the first instalment of a comprehensive endeavour to catalogue and detail the epigenetic effects of compounds derived from Olea Europaea.
authors.affiliation: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, 3004, Australia. tom.karagiannis@bakeridi.edu.au.
authors.forename: Natalie P
authors.initials: NP
authors.lastname: Bonvino
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Ray
authors.forename: Vi T
authors.initials: VT
authors.lastname: Luu
authors.forename: Julia
authors.initials: J
authors.lastname: Liang
authors.forename: Andrew
authors.initials: A
authors.lastname: Hung
authors.forename: Tom C
authors.initials: TC
authors.lastname: Karagiannis