A method to identify all modifications on histones, the proteins around which DNA is packed, is presented online in Nature Methods. This study should allow researchers a better understanding of how genes are regulated by alterations to these proteins.
DNA holds all the information for the building blocks of life, but how a cell reads this genetic information depends on histones, and in particular on modifications to these histones. For example, the attachment of methyl groups to histones usually signals that a gene is silent, whereas the attachment of acetyl groups corresponds to gene activation. Scientists have dubbed the combinatorial use of histone modifications the 'histone code,' but the extent to which different modifications are combined in the histone code is still unknown.
To help crack the code, Neil Kelleher and colleagues devised a method to identify all the possible modifications that occur on histones in a cell. First they separated different histone variants, depending on their degree of acetylation and methylation, by hydrophilic interaction chromatography, then they applied high-resolution tandem mass spectroscopy to identify all modifications on each variant and the exact residues carrying them. By using a mass spectrometry technique known as 'top down,' in which intact proteins are fragmented inside the mass spectrometer, they observed better preservation of modifications than traditional mass spectrometry methods looking at pre-digested proteins. For one particular histone alone, they found over 150 different patterns of modification.
This method helps to decipher the elements that make up the histone code and will allow researchers to relate the pattern of these modifications to the regulation of gene activity.
Neil Kelleher (University of Illinois at Urbana-Champaign, IL, USA)
Abstract available online.
(C) Nature Methods press release.
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