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Template:STRUCTURE 2vpg

DECODING OF METHYLATED HISTONE H3 TAIL BY THE PYGO-BCL9 WNT SIGNALING COMPLEX

Overview

Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional activity of beta-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.

About this Structure

2VPG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex., Fiedler M, Sanchez-Barrena MJ, Nekrasov M, Mieszczanek J, Rybin V, Muller J, Evans P, Bienz M, Mol Cell. 2008 May 23;30(4):507-18. PMID:18498752 Page seeded by OCA on Wed Jun 18 12:05:23 2008