Mass spectrometry in epigenetic research.
The inhibition of the histone deacetylase enzymes induces hyperacetylation of the histone proteins. This hyperacetylation causes cell cycle arrest and cell death in cancer cells but not in normal cells. Therefore, the development of histone deacetylase inhibitors for the treatment of various cancers has gained tremendous interest in recent years, and many of these inhibitors are currently undergoing clinical trials. Despite intense research, however, the exact molecular mechanisms of action of these molecules remain, to a wide extent, unclear. The recent application of mass spectrometry-based proteomics techniques to histone biology has gained new insight into the function of the nucleosome: Novel posttranslational modifications have been discovered at the lateral surface of the nucleosome. These modifications regulate histone-DNA interactions, adding a new dimension to the epigenetic regulation of nucleosome mobility.
Beck
Hans Christian
HC
Teknologisk Institut, Kolding, Denmark.
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics; D012106:Research
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases