Histone ubiquitylation control of gene expression

Abstract

In addition to chemical modifications such as acetylation or methylation, histones are modified by the addition of small polypeptides such as ubiquitin. Whereas poly-ubiquitylation generally targets proteins for proteasomal degradation, histones are predominantly mono-ubiquitylated. Histone mono-ubiquitylation regulates nuclear processes that include transcription and DNA damage responses. The carboxy-terminal tails of histones H2A and H2B provide the major sites for mono-ubiquitylation. However, recent studies have identified mono-ubiquitylated residues on the amino-terminal tails of H2A and H2B. These include novel lysines that are ubiquitylated in response to DNA damage. In this review, first the enzymes that deposit and remove ubiquitin from histones are described. Although these enzymes are best characterized with respect to histone ubiquitylation, a number of these enzymes have other substrates that might play an important role in their cellular activities. Second, the role of H2A and H2B mono-ubiquitylation in gene expression is discussed; whereas H2B mono-ubiquitylation activates transcription initiation and elongation, H2A mono-ubiquitylation promotes transcription repression. Finally, regulation of histone ubiquitylation during the DNA damage response and in the cell cycle is described.