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Publication Abstract from PubMed

Functional crosstalk between the promoter and terminator of a gene has long been noted. Promoters and terminators are juxtaposed to form gene loops in several organisms and gene looping is thought to be involved in transcriptional regulation. The general transcription factor II B (TFIIB) and the C-terminal domain phosphatase Ssu72, essential factors of the transcription pre-initiation complex and the mRNA processing and polyadenylation complex, respectively, are important for gene loop formation. TFIIB and Ssu72 interact both genetically and physically, but the molecular basis of this interaction is not known. Here we present a crystal structure of the core domain of TFIIB in two new conformations that differ in the relative distance and orientation of the two cyclin-like domains. The observed extraordinary conformational plasticity may underlie the binding of TFIIB to multiple transcription factors and promoter DNAs that occurs in distinct stages of transcription including initiation, reinitiation and gene looping. We mapped the binding interface of the TFIIB-Ssu72 complex using a series of systematic, structure-guided in vitro binding and site-specific photocrosslinking assays. Our results indicate that Ssu72 competes with acidic activators for TFIIB binding and that Ssu72 disrupts an intramolecular TFIIB complex known to impede transcription initiation. We also show that the TFIIB binding site on Ssu72 overlaps with the binding site of symplekin, a component of the mRNA processing and polyadenylation complex. We propose a hand-off model in which Ssu72 mediates a conformational transition in TFIIB, accounting for the role of Ssu72 in transcription reinitiation, gene looping and promoter-terminator crosstalk.

Structural dissection of an interaction between transcription initiation and termination factors implicated in promoter-terminator crosstalk.,Bratkowski M, Unarta IC, Zhu L, Shubbar M, Huang X, Liu X J Biol Chem. 2017 Nov 20. pii: M117.811521. doi: 10.1074/jbc.M117.811521. PMID:29158257^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.