Histone ubiquitination: a tagging tail unfolds?

Abstract

Despite the fact that histone H2A ubiquitination affects about 10-15% of this histone in most eukaryotic cells, histone ubiquitination is among one of the less-well-characterized post-translational histone modifications. Nevertheless, some important observations have been made in recent years. Whilst several enzymes had been known to ubiquitinate histones in vitro, recent studies in yeast have led to the unequivocal identification of the enzyme responsible for this post-translational modification in this organism. A strong functional co-relation to meiosis and spermiogenesis has also now been well documented, although its participation in other functional aspects of chromatin metabolism, such as transcription or DNA repair, still remains rather speculative and controversial. Because of its nature, histone ubiquitination represents the most bulky structural change to histones and as such it would be expected to exert an important effect on chromatin structure. Past and recent structural studies, however, indicate a surprising lack of effect of (H2A/H2B) ubiquitination on nucleosome architecture and of uH2A on chromatin folding. These results suggest that this modification may serve as a signal for recognition by functionally relevant trans-acting factors and/or operate synergistically in conjunction with other post-translational modifications such as for instance acetylation.

The role of the ubiquitin/proteasome system in cellular responses to radiation

“…Disruption of histone Ubiquitinylation is known to lead to defects in DNA repair (Robzyk et al, 2000). The roles that have been proposed for histone Ub are, however, multiple and complex, extending from chromatin uncoiling and gene transcription to gene silencing (Sun and Allis, 2002), and remain controversial (Jason et al, 2002).…”

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

“…Covalent modification can occur at both the DNA and histone levels. With histones, modifications include acetylation, phosphorylation, methylation, ubiquitination, and many others (for reviews, see Spencer and Davie, 1999;Strahl and Allis, 2000;Berger, 2002;Jason et al, 2002;Kouzarides, 2007). Different modifications interplay with each other and contribute significantly to the formation of a complex epigenetic program for generating and preserving the defined chromatin state of a given cell type.…”

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

“…Some early studies suggested the involvement of H2A ubiquitylation in gene activation (for review, see Jason et al 2002); however, recent studies have indicated a role for H2A ubiquitylation in gene repression (for reviews, see Zhang 2003;Shilatifard 2006). An H2A ubiquitin ligase was identified, and its complex has been suggested to play a role in Polycomb group (PcG) protein-mediated gene silencing by H2A ubiquitylation (Wang et al 2004).…”