1. Structural Insight into the Recognition of the H3K4me3 Mark by the TFIID Subunit TAF3
- Author
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Annemarie C. Dechesne, Frederik M. A. van Schaik, Hans Wienk, Joost Ballering, Holger Rehmann, Hugo van Ingen, John A.W. Kruijzer, H. Th. Marc Timmers, Rob M. J. Liskamp, and Rolf Boelens
- Subjects
Models, Molecular ,DNA Mutational Analysis ,Biology ,Methylation ,Protein Structure, Secondary ,Conserved sequence ,Histones ,Mice ,Histone H3 ,Protein structure ,Structural Biology ,Animals ,Humans ,Histone code ,Nuclear Magnetic Resonance, Biomolecular ,Molecular Biology ,Homeodomain Proteins ,Genetics ,TATA-Binding Protein Associated Factors ,General transcription factor ,Protein Structure, Tertiary ,Cell biology ,Protein Subunits ,TAF1 ,Multiprotein Complexes ,H3K4me3 ,Transcription Factor TFIID ,Transcription factor II D ,Peptides ,Protein Binding - Abstract
Trimethylation of lysine residue K4 of histone H3 (H3K4me3) strongly correlates with active promoters for RNA polymerase II-transcribed genes. Several reader proteins, including the basal transcription factor TFIID, for this nucleosomal mark have been identified. Its TAF3 subunit specifically binds the H3K4me3 mark via its conserved plant homeodomain (PHD) finger. Here, we report the solution structure of the TAF3-PHD finger and its complex with an H3K4me3 peptide. Using a combination of NMR, mutagenesis, and affinity measurements, we reveal the structural basis of binding affinity, methylation-state specificity, and crosstalk with asymmetric dimethylation of R2. A unique local structure rearrangement in the K4me3-binding pocket of TAF3 due to a conserved sequence insertion underscores the requirement for cation-pi interactions by two aromatic residues. Interference by asymmetric dimethylation of arginine 2 suggests that a H3R2/K4 "methyl-methyl" switch in the histone code dynamically regulates TFIID-promoter association.
- Published
- 2008