Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription

DNA is a very long molecule, so it needs to be packaged carefully to fit into the nucleus of a cell. To achieve this, the DNA is wrapped around proteins called histones to form a structure termed a nucleosome, which is the building block of a more compacted substance called chromatin. However, to express the genes in the DNA it is necessary to open up parts of the chromatin to give various enzymes access to the DNA. Cells often chemically modify histones by adding acetyl or methyl groups, and these modifications are known to influence what proteins can bind to the nucleosomes, which ultimately influences what genes are expressed in the cell at a given time. It has been suspected for some time that histone modifications can also influence gene expression more directly, but there has been little evidence for this idea. Now Di Cerbo et al. have studied what happens when acetyl or methyl groups are added to a specific site within a histone called H3K64, which is close to where the DNA wraps around this histone. These experiments showed that this site tends to be acetylated when a nearby gene is active, and to be unmodified or methylated when this gene is not active. It appears that the addition of the acetyl group makes this region of the chromatin less stable: this, in turn, makes it easier for the chromatin to be unpacked, thus giving access to the enzymes that transcribe the DNA and allowing transcription to take place. The work of Di Cerbo et al. shows that methylation and acetylation at the same site within a histone can define two opposing states of chromatin and DNA: an active state and a repressive state.