title: The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex.
abstract: Covalent modifications of the histone tails and the cross talk between these modifications are hallmark features of gene regulation. The SAGA histone acetyltransferase complex is one of the most well-characterized complexes involved in these covalent modifications. The recent finding that the removal of the ubiquitin group from H2B is performed by a component of SAGA, Ubp8, is intriguing as it assigns two posttranslation modification processes to one complex. In this work, we characterize the association of Ubp8 with SAGA and the effect that acetylation and deubiquitylation have on one another in vitro and in vivo. We found not only that Ubp8 is a part of the SAGA complex, but also that its deubiquitylation activity requires Ubp8's association with SAGA. Furthermore, we found that the Ubp8 association with SAGA requires Sgf11 and that this requirement is reciprocal. We also found that the acetylation and deubiquitylation activities of SAGA are independent of one another. However, we found that preacetylating histone H2B inhibited subsequent deubiquitylation. Additionally, we found that increasing the ubiquitylation state of H2B inhibited the expression of the ARG1 gene, whose repression was previously shown to require the RAD6 ubiquitin ligase. Taken together, these data indicate that the expression of some genes, including ARG1, is regulated by a balance of histone H2B ubiquitylation in the cell.
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Lee
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000107:Acetylation; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D006657:Histones; C489245:SGF11 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025801:Ubiquitin