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.