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Title: Polycomb-like proteins link the PRC2 complex to CpG islands

Abstract

The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression1,2 and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components3, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci4,5,6,7,8,9,10,11,12,13. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation14. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCLmore » proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.« less

Authors:
; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGN
OSTI Identifier:
1409104
Resource Type:
Journal Article
Journal Name:
Nature (London)
Additional Journal Information:
Journal Volume: 549; Journal Issue: 7671; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; 58 GEOSCIENCES

Citation Formats

Li, Haojie, Liefke, Robert, Jiang, Junyi, Kurland, Jesse Vigoda, Tian, Wei, Deng, Pujuan, Zhang, Weidi, He, Qian, Patel, Dinshaw J., Bulyk, Martha L., Shi, Yang, and Wang, Zhanxin. Polycomb-like proteins link the PRC2 complex to CpG islands. United States: N. p., 2017. Web. doi:10.1038/nature23881.
Li, Haojie, Liefke, Robert, Jiang, Junyi, Kurland, Jesse Vigoda, Tian, Wei, Deng, Pujuan, Zhang, Weidi, He, Qian, Patel, Dinshaw J., Bulyk, Martha L., Shi, Yang, & Wang, Zhanxin. Polycomb-like proteins link the PRC2 complex to CpG islands. United States. doi:10.1038/nature23881.
Li, Haojie, Liefke, Robert, Jiang, Junyi, Kurland, Jesse Vigoda, Tian, Wei, Deng, Pujuan, Zhang, Weidi, He, Qian, Patel, Dinshaw J., Bulyk, Martha L., Shi, Yang, and Wang, Zhanxin. Wed . "Polycomb-like proteins link the PRC2 complex to CpG islands". United States. doi:10.1038/nature23881.
@article{osti_1409104,
title = {Polycomb-like proteins link the PRC2 complex to CpG islands},
author = {Li, Haojie and Liefke, Robert and Jiang, Junyi and Kurland, Jesse Vigoda and Tian, Wei and Deng, Pujuan and Zhang, Weidi and He, Qian and Patel, Dinshaw J. and Bulyk, Martha L. and Shi, Yang and Wang, Zhanxin},
abstractNote = {The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression1,2 and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components3, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci4,5,6,7,8,9,10,11,12,13. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation14. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.},
doi = {10.1038/nature23881},
journal = {Nature (London)},
issn = {0028-0836},
number = 7671,
volume = 549,
place = {United States},
year = {2017},
month = {9}
}

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