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General transcription factor TFIID is a cornerstone of RNA polymerase II transcription initiation in eukaryotic cells. How human TFIID-a megadalton-sized multiprotein complex composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs)-assembles into a functional transcription factor is poorly understood. Here we describe a heterotrimeric TFIID subcomplex consisting of the TAF2, TAF8 and TAF10 proteins, which assembles in the cytoplasm. Using native mass spectrometry, we define the interactions between the TAFs and uncover a central role for TAF8 in nucleating the complex. X-ray crystallography reveals a non-canonical arrangement of the TAF8-TAF10 histone fold domains. TAF2 binds to multiple motifs within the TAF8 C-terminal region, and these interactions dictate TAF2 incorporation into a core-TFIID complex that exists in the nucleus. Our results provide evidence for a stepwise assembly pathway of nuclear holo-TFIID, regulated by nuclear import of preformed cytoplasmic submodules.

Original publication

DOI

10.1038/ncomms7011

Type

Journal article

Journal

Nat Commun

Publication Date

14/01/2015

Volume

6

Keywords

Amino Acid Motifs, Calorimetry, Cell Nucleus, Crystallography, X-Ray, Cytoplasm, HeLa Cells, Histones, Humans, Mass Spectrometry, Models, Molecular, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Recombinant Proteins, Surface Plasmon Resonance, TATA-Binding Protein Associated Factors, Transcription Factor TFIID, Transcription Factors