By: Marc Timmers, Deutsche Konsortium für Translationelles Krebsforschung (DKTK) standort Freiburg, Germany
Title: Building Transcrition Complexes

Cancer genome sequencing programs revealed recurring mutations in subunits of large and heterogeneous multi-subunit complexes, which regulate epigenetic and transcriptional processes. These subunits are often shared between complexes of distinct function. The basal transcription factor TFIID and the SAGA co-activator complex are examples of this theme. The crucial functions of TFIID and SAGA are reflected in their structural complexity, shared and unique subunits and diverse biochemical activities. Insights into in vivo assembly pathways of TFIID, SAGA and related transcription and chromatin complexes have been rather limited.

Recent cryo-EM data of yeast and human TFIID showed that the WD-40 domain of TAF5 organizes the histone-fold dimers of other TAFs into separate lobes. We have been employing quantitative mass spectrometry (qMS) methods to examine TFIID submodules and assembly mechanisms in human cells. This led to the identification of a submodule consisting of TAF5, TAF6 and TAF9 and to the discovery of a checkpoint function for chaperonin TRiC/CCT in TAF5/6/9 subcomplex assembly. Next, we employed qMS to interrogate cytoplasmic, nuclear and chromatin fractions from all 18 TFIID-TAFs entry points. I will discuss the progress in our understanding of TFIID biogenesis from TAF subcomplexes and of the dynamic association of TFIID and SAGA to chromatin.