TY - JOUR
T1 - Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export
AU - Köhler, Alwin
AU - Schneider, Maren
AU - Cabal, Ghislain G.
AU - Nehrbass, Ulf
AU - Hurt, Ed
N1 - Funding Information:
We thank Sabine Merker, Petra Ihrig and J. Lechner for performing mass spectrometry; Heiner Sähr for technical assitance and Silke Hauf (Max-Planck-Institut, Tübingen), Suzanne Elsasser, Dan Finley (Harvard Medical School, Boston) and Dieter Kressler for comments on the mansucript. We thank Mary Ann Osley for yeast strains and Catherine Dargemont for the GAL1 RNA probe. E.H. is a recipient of grants from the Deutsche Forschungsgemeinschaft (Leibniz Programme, SFB 638/B3) and Fonds der Chemischen Industrie. G.G.C. is a recipient of a fellowship from the Association pour la Researche sur le Cancer (ARC).
PY - 2008/6
Y1 - 2008/6
N2 - Targeting of a gene to the nuclear pore complexes (NPCs), known as gene gating, can affect its transcriptional state. However, the mechanism underlying gene gating is poorly understood. Here, we have identified SAGA-associated Sgf73 (ref. 10), the yeast orthologue of human Ataxin-7 (ref. 11), as a regulator of histone H2B ubiquitin levels, a modification linked to both transcription initiation and elongation. Sgf73 is a key component of a minimal histone-deubiquitinating complex. Activation of the H2B deubiquitinating protease, Ubp8, is cooperative and requires complex formation with the amino-terminal zinc-finger-containing domain of Sgf73 and Sgf11-Sus1. Through a separate domain, Sgf73 mediates recruitment of the TREX-2 mRNA export factors Sac3 and Thp1 to SAGA and their stable interaction with Sus1-Cdc31. This latter step is crucial to target TREX-2 to the NPC. Loss of Sgf73 from SAGA abrogates gene gating of GAL1 and causes a GAL1 mRNA export defect. Thus, Sgf73 provides a molecular scaffold to integrate the regulation of H2B ubiquitin levels, tethering of a gene to the NPC and export of mRNA.
AB - Targeting of a gene to the nuclear pore complexes (NPCs), known as gene gating, can affect its transcriptional state. However, the mechanism underlying gene gating is poorly understood. Here, we have identified SAGA-associated Sgf73 (ref. 10), the yeast orthologue of human Ataxin-7 (ref. 11), as a regulator of histone H2B ubiquitin levels, a modification linked to both transcription initiation and elongation. Sgf73 is a key component of a minimal histone-deubiquitinating complex. Activation of the H2B deubiquitinating protease, Ubp8, is cooperative and requires complex formation with the amino-terminal zinc-finger-containing domain of Sgf73 and Sgf11-Sus1. Through a separate domain, Sgf73 mediates recruitment of the TREX-2 mRNA export factors Sac3 and Thp1 to SAGA and their stable interaction with Sus1-Cdc31. This latter step is crucial to target TREX-2 to the NPC. Loss of Sgf73 from SAGA abrogates gene gating of GAL1 and causes a GAL1 mRNA export defect. Thus, Sgf73 provides a molecular scaffold to integrate the regulation of H2B ubiquitin levels, tethering of a gene to the NPC and export of mRNA.
UR - https://www.scopus.com/pages/publications/44649179312
U2 - 10.1038/ncb1733
DO - 10.1038/ncb1733
M3 - Article
C2 - 18488019
AN - SCOPUS:44649179312
SN - 1465-7392
VL - 10
SP - 707
EP - 715
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 6
ER -