Structural changes in TAF4b-TFIID correlate with promoter selectivity.
Proper ovarian development requires the cell type-specific transcription factor TAF4b, a subunit of the core promoter recognition complex TFIID. We present the 35 A structure of a cell type-specific core promoter recognition complex containing TAF4b and TAF4 (4b/4-IID), which is responsible for directing transcriptional synergy between c-Jun and Sp1 at a TAF4b target promoter. As a first step toward correlating potential structure/function relationships of the prototypic TFIID versus 4b/4-IID, we have compared their 3D structures by electron microscopy and single-particle reconstruction. These studies reveal that TAF4b incorporation into TFIID induces an open conformation at the lobe involved in TFIIA and putative activator interactions. Importantly, this open conformation correlates with differential activator-dependent transcription and promoter recognition by 4b/4-IID. By combining functional and structural analysis, we find that distinct localized structural changes in a megadalton macromolecular assembly can significantly alter its activity and lead to a TAF4b-induced reprogramming of promoter specificity.
Liu
Wei-Li
WL
Howard Hughes Medical Institute, Li Ka-Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Coleman
Robert A
RA
Grob
Patricia
P
King
David S
DS
Florens
Laurence
L
Washburn
Michael P
MP
Geles
Kenneth G
KG
Yang
Joyce L
JL
Ramey
Vincent
V
Nogales
Eva
E
Tjian
Robert
R
D001402:B-Lymphocytes; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008854:Microscopy, Electron; D008958:Models, Molecular; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D035561:Transcription Factor TFIIA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D035362:Transcription Factor TFIID / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D015533:Transcriptional Activation
D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; C101881:TAF4B protein, human; D035381:TATA-Binding Protein Associated Factors; D035561:Transcription Factor TFIIA; D035362:Transcription Factor TFIID