Sumoylation controls the timing of Tup1-mediated transcriptional deactivation

Chong Han Ng, Akhi Akhter, Nathan Yurko, Justin M. Burgener, Emanuel Rosonina () and James L. Manley ()
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Chong Han Ng: Columbia University, 1212 Amsterdam Avenue, 1117 Fairchild Center, New York, New York 10027, USA
Akhi Akhter: York University
Nathan Yurko: Columbia University, 1212 Amsterdam Avenue, 1117 Fairchild Center, New York, New York 10027, USA
Justin M. Burgener: York University
Emanuel Rosonina: York University
James L. Manley: Columbia University, 1212 Amsterdam Avenue, 1117 Fairchild Center, New York, New York 10027, USA

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract The small ubiquitin-like modifier (SUMO) is implicated in various cellular activities, including transcriptional regulation. We previously showed that the yeast activator Gcn4 becomes sumoylated during activation, facilitating its eventual promoter eviction and transcriptional shut off. Here we show that the corepressor Tup1 is sumoylated, at two specific lysines, under various stress conditions. Mutation of these sites has no effect on Tup1 recruitment or RNAP II promoter occupancy immediately following induction. However, Tup1 levels subsequently decrease, while RNAP II and transcription increase in Tup1 mutant cells. Consistent with this, a Tup1 mutant displaying increased sumoylation led to reduced transcription. We also show that coordinated sumoylation of Gcn4 and Tup1 enhances Gcn4 promoter eviction and that multiple Tup1-interacting proteins become sumoylated after stress. Together, our studies provide evidence that coordinated sumoylation of Gcn4, Tup1 and likely other factors dampens activated transcription by stabilizing Tup1 binding and stimulating Gcn4 and RNAP II removal.

Date: 2015
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DOI: 10.1038/ncomms7610

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