Multivalent Role of Human TFIID in Recruiting Elongation Components at the Promoter-Proximal Region for Transcriptional Control

Cell Rep. 2019 Jan 29;26(5):1303-1317.e7. doi: 10.1016/j.celrep.2019.01.012.

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. In vitro 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.

Keywords: AF9; P-TEFb; TAF6; TFIID; elongation; pause; poly-Ser; super elongation complex; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA / metabolism
  • Gene Expression Regulation
  • Humans
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Domains
  • Protein Subunits / metabolism
  • Templates, Genetic
  • Transcription Elongation, Genetic*
  • Transcription Factor TFIID / metabolism*
  • Transcription, Genetic*

Substances

  • Protein Subunits
  • Transcription Factor TFIID
  • DNA