Abstract
Despite substantial progress in our understanding of the players involved and the regulatory mechanisms controlling the initiation and elongation steps of transcription, little is known about the recruitment of elongation factors at promoter-proximal regions for the initiation-to-elongation transition. Here, we show evidence that human TFIID, which initiates pre-initiation complex (PIC) assembly, contributes to regulating the recruitment of super-elongation complex (SEC) components at the promoter-proximal region through interactions among selective TAF and SEC components. Invitro direct interactions, coupled with cell-based assays, identified an important poly-Ser domain within SEC components that are involved in their interaction with TFIID. DNA template-based recruitment assays, using purified components, further show a direct role for poly-Ser domain-dependent TFIID interaction in recruiting SEC components on target DNA. Consistently, ChIP and RNA analyses have shown the importance of this mechanism in TFIID-dependent SEC recruitment and target gene expression within mammalian cells.
Highlights
The initiation step of RNA polymerase II (Pol II hereafter)driven eukaryotic transcription begins with activator-dependent recruitment of TATA-binding protein (TBP)-containing TFIID complex (TFIID hereafter) at the promoter region
Human TFIID contains $14 other TBP-associated factors (TAFs) that help in recruiting TFIID and other general transcription factors (GTFs) at the promoter region for assisting pre-initiation complex (PIC) assembly
It is widely believed that the phosphorylation activity of positive transcription elongation factor b (P-TEFb) complex helps in relieving the paused Pol II to facilitate its entry into productive elongation
Summary
The initiation step of RNA polymerase II (Pol II hereafter)driven eukaryotic transcription begins with activator-dependent recruitment of TATA-binding protein (TBP)-containing TFIID complex (TFIID hereafter) at the promoter region. Human TFIID contains $14 other TBP-associated factors (TAFs) that help in recruiting TFIID and other general transcription factors (GTFs) at the promoter region for assisting pre-initiation complex (PIC) assembly. It is widely believed that the phosphorylation activity of positive transcription elongation factor b (P-TEFb) complex helps in relieving the paused Pol II to facilitate its entry into productive elongation. The NELF complex loses its ability to interact with the nascent RNA as well as the inhibitory DSIF complex and thereby relieves the paused Pol II to enter into productive elongation (Yamaguchi et al, 2013)
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