In the nucleus of mammals and yeast, DNA is packaged by forming complexes with histone proteins in a structure called the nucleosome, the basic building block of chromatin. The tails of the histones protrude from the nucleosome and can be marked on many amino acid residues by chemical modifications such as methylation and acetylation. A highly studied modification, which is robustly associated with active gene promoters, is histone H3 lysine 4 methylation. We describe here a novel modification, histone H3 lysine 4 acetylation (H3K4ac), which can occur on the same lysine of the histone H3 tail (but not at the same time as methylation). We have identified the enzymes responsible for depositing and removing this mark and mapped its distribution throughout the yeast genome. We found that H3K4ac is present on active genes and is important for the full expression of a subset of them. Strikingly, H3K4 methylation was found in the same promoters as H3K4ac and contributes to regulate the abundance and localisation of H3K4ac. This example of cross-talk between two different modifications of the same residue has fundamental implications for understanding how genes are activated and how their packaging in the nucleus controls this process.
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