Unknown

Dataset Information

0

Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1.


ABSTRACT: Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and H3R8me2a are recognized using an "insertion cavity" recognition mode, contributing to a methylation state-specific layer of regulation. In vivo functional studies suggest that Spindlin1 activates Wnt/?-catenin signaling downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex, which together are capable of generating a specific H3 "K4me3-R8me2a" pattern. Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes. Taken together, our work connects a histone "lysine-arginine" methylation pattern readout by Spindlin1-to-Wnt signaling at the transcriptional level.

SUBMITTER: Su X 

PROVIDER: S-EPMC3967050 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1.

Su Xiaonan X   Zhu Guixin G   Ding Xiaozhe X   Lee Shirley Y SY   Dou Yali Y   Zhu Bing B   Wu Wei W   Li Haitao H  

Genes & development 20140303 6


Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats  ...[more]

Similar Datasets

| S-EPMC7864079 | biostudies-literature
| S-EPMC3497761 | biostudies-literature
| S-EPMC5546304 | biostudies-literature
| S-EPMC3014276 | biostudies-literature
| S-EPMC2141896 | biostudies-literature
| S-EPMC9768651 | biostudies-literature
| S-EPMC3052887 | biostudies-literature
| S-EPMC3098377 | biostudies-literature
| S-EPMC4627087 | biostudies-other
| S-EPMC2700282 | biostudies-literature