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Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex

DOI: 10.1016/j.molcel.2008.03.011 DOI Help
PMID: 18498752 PMID Help

Authors: Marc Fiedler (Universiy of Cambridge) , María José Sánchez-barrena (Universiy of Cambridge) , Maxim Nekrasov (EMBL) , Juliusz Mieszczanek (Universiy of Cambridge) , Vladimir Rybin (EMBL) , Jürg Müller (EMBL) , Phil Evans (Universiy of Cambridge) , Mariann Bienz (Universiy of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 30 (4) , PAGES 507 - 518

State: Published (Approved)
Published: May 2008

Open Access Open Access

Abstract: 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.

Journal Keywords: Signal; Amino; Animals; Binding; Crystallography; X-Ray; Drosophila; Drosophila; Histones; Humans; Intracellular; Lysine; Methylation; Models; Molecular; Multiprotein; Neoplasm; Peptides; Protein; Recombinant; Sequence; Signal; Wnt Proteins

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Other Facilities: ESRF

Added On: 18/11/2015 13:30

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