1. Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex
- Author
-
Jürg Müller, Marc Fiedler, Juliusz Mieszczanek, Mariann Bienz, Maxim Nekrasov, María José Sánchez-Barrena, Phil Evans, and Vladimir Rybin
- Subjects
Models, Molecular ,Protein Conformation ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Crystallography, X-Ray ,Methylation ,Article ,Histones ,Histone H3 ,Histone H2A ,Animals ,Drosophila Proteins ,Humans ,Histone code ,Amino Acid Sequence ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Histone binding ,Regulation of gene expression ,Binding Sites ,biology ,Lysine ,Intracellular Signaling Peptides and Proteins ,DNA ,Cell Biology ,Molecular biology ,Neoplasm Proteins ,Cell biology ,Wnt Proteins ,Drosophila melanogaster ,Histone ,SIGNALING ,PHD finger ,Multiprotein Complexes ,Histone methyltransferase ,biology.protein ,Peptides ,Sequence Alignment ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
Summary Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional activity of β-catenin/Armadillo in normal and malignant cells. We show that human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains from BCL9/Legless to bind specifically to the histone H3 tail methylated at lysine 4 (H3K4me). The crystal structures of ternary complexes between PHD, HD1, and two different H3K4me peptides reveal a unique mode of histone tail recognition: efficient histone binding requires HD1 association, and the PHD-HD1 complex binds preferentially to H3K4me2 while displaying insensitivity to methylation of H3R2. Therefore, this is a prime example of histone tail binding by a PHD finger (of Pygo) being modulated by a cofactor (BCL9/Legless). Rescue experiments in Drosophila indicate that Wnt signaling outputs depend on histone decoding. The specificity of this process provided by the Pygo-BCL9/Legless complex suggests that this complex facilitates an early step in the transition from gene silence to Wnt-induced transcription.
- Published
- 2008
- Full Text
- View/download PDF