Histone ubiquitylation and the regulation of transcription.
The small (76 amino acids) and highly conserved ubiquitin protein plays key roles in the physiology of eukaryotic cells. Protein ubiquitylation has emerged as one of the most important intracellular signaling mechanisms, and in 2004 the Nobel Prize was awarded to Aaron Ciechanower, Avram Hersko, and Irwin Rose for their pioneering studies of the enzymology of ubiquitin attachment. One of the most common features of protein ubiquitylation is the attachment of polyubiquitin chains (four or more ubiquitin moieties attached to each other), which is a widely used mechanism to target proteins for degradation via the 26S proteosome. However, it is noteworthy that the first ubiquitylated protein to be identified was histone H2A, to which a single ubiquitin moiety is most commonly attached. Following this discovery, other histones (H2B, H3, H1, H2A.Z, macroH2A), as well as many nonhistone proteins, have been found to be monoubiquitylated. The role of monoubiquitylation is still elusive because a single ubiquitin moiety is not sufficient to target proteins for turnover, and has been hypothesized to control the assembly or disassembly of multiprotein complexes by providing a protein-binding site. Indeed, a number of ubiquitin-binding domains have now been identified in both polyubiquitylated and monoubiquitylated proteins. Despite the early discovery of ubiquitylated histones, it has only been in the last five or so years that we have begun to understand how histone ubiquitylation is regulated and what roles it plays in the cell. This review will discuss current research on the factors that regulate the attachment and removal of ubiquitin from histones, describe the relationship of histone ubiquitylation to histone methylation, and focus on the roles of ubiquitylated histones in gene expression.
Osley
Mary Ann
MA
Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA. mosley@salud.unm.edu
Fleming
Alastair B
AB
Kao
Cheng-Fu
CF
D000818:Animals; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D006657:Histones; D025801:Ubiquitin