Novel tales of histone tails

Abstract

Since the discovery in 1996 that histone acetylation and deacetylation are catalysed by transcription factors, the transcription and chromatin fields have merged. Indeed, the mechanisms and consequences of covalent histone modifications have taken center stage. Acetylation of the N-terminal tails of histones H3 and H4 has occupied the limelight, although N-terminal phosphorylation of H3 and its effect on chromosome dynamics has assumed a prominent role. Much less attention has been directed toward ubiquitination, ADP-ribosylation and methylation, histone modifications the functional consequences of which have remained obscure. This is about to change with recent reports of two novel histone modifications in yeast. Robzyk et al.1 Robzyk K. et al. Rad6-dependent ubiquitination of histone H2B in yeast. Science. 2000; 287: 501-504 Crossref PubMed Scopus (522) Google Scholar used a sensitive immunoassay to reinvestigate a decade-old report that yeast histones are not ubiquitinated. They report that histone H2B is in fact ubiquitinated, representing as much as 10% of total cellular H2B. A single molecule of ubiquitin is attached to a lysine residue (K123) near the C-terminus of H2B, catalysed by the ubiquitin-conjugating enzyme Rad6. A substitution of K123 eliminated H2B ubiquitination and resulted in mitotic and meiotic growth defects, demonstrating the functional relevance of histone ubiquitination in vivo. In the other paper, Tanny et al.2 Tanny J.C. et al. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell. 1999; 99: 735-745 Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar identified an enzymatic activity for Sir2, a protein essential for silencing in yeast. Remarkably, Sir2 was found to be an NAD-dependent ADP-ribosyltransferase, able to modify itself, as well as histones, in vitro. The enzymatic activity of Sir2 is required for silencing in vivo, but not for the association of Sir2 with chromatin. These results define a chromatin-associated enzymatic activity that is essential for silencing and raise the interesting possibility that silencing might be regulated by the cellular redox state. The histone substrate specificity of Sir2 and whether the Sir2 requirement for silencing is actually a consequence of histone ADP-ribosylation remain to be determined. Regardless, both papers highlight the diversity of covalent histone modifications and expand the repertoire of mechanisms controlling chromosome function in eukaryotic cells.