Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: Distinct roles in telomeric silencing and general chromatin

被引:122
作者
Gardner, RG [1 ]
Nelson, ZW [1 ]
Gottschling, DE [1 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
关键词
D O I
10.1128/MCB.25.14.6123-6139.2005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously discovered that the ubiquitin protease Ubp10/Dot4p is important for telomeric silencing through its interaction with Sir4p. However, the mechanism of Ubp10p action was unknown. We now provide evidence that Ubp10p removes ubiquitin from histone H2B; cells with UBP10 deleted have increased steady-state levels of H2B ubiquitination. As a consequence, ubp10 Delta cells also have increased steady-state levels of histone H3 Lys4 and Lys79 methylation. Consistent with its role in silencing, Ubp10p is preferentially localized to silent chromatin where its ubiquitin protease activity maintains low levels of 113 Lys4 and Lys79 methylation to allow optimal Sir protein binding to telomeres and global telomeric silencing. The ubiquitin protease Ubp8p has also been shown to remove ubiquitin from H2B, and ubp8 Delta cells have increased steady-state levels of H2B ubiquitination similar to those in ubp10 Delta cells. Unlike ubp10 Delta cells, however, ubp8 Delta cells do not have increased steady-state levels of H3 Lys4 and Lys79 methylation, nor is telomeric silencing affected. Despite their separate functions in silencing and SAGA-mediated transcription, respectively, deletion of both UBP10 and UBP8 results in a synergistic increase in the steady-state levels of H2B ubiquitination and in the number of genes with altered expression, indicating that Ubp10p and Ubp8p likely overlap in some of their target chromatin regions. We propose that Ubp10p and Ubp8p are the only ubiquitin proteases that normally remove monoubiquitin from histone H2B and, while there are regions of the genome to which each is specifically targeted, both combine to regulate the global balance of H2B ubiquitination.
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页码:6123 / 6139
页数:17
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