Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex
详细信息 查看全文
- 作者：Marc Fiedler ; Marí ; a José ; Sá ; nchez-Barrena ; Maxim Nekrasov ; Juliusz Mieszczanek ; Vladimir Rybin ; Jü ; rg Mü ; ller ; Phil Evans ; Mariann Bienz
- 关键词：DNA ; SIGNALING
- 刊名：Molecular Cell
- 出版年：2008
- 出版时间：23 May 2008
- 年：2008
- 卷：30
- 期：4
- 页码：507-518
- 全文大小：1821 K
文摘
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.