Polycomb-like proteins link the PRC2 complex to CpG islands
The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression 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 t...
| Κύριοι συγγραφείς: | , , , , , , , , , , , |
|---|---|
| Μορφή: | Journal article |
| Γλώσσα: | English |
| Έκδοση: |
Springer Nature
2017
|
| _version_ | 1826271764096745472 |
|---|---|
| author | Li, H Liefke, R Jiang, J Kurland, JV Tian, W Deng, P Zhang, W He, Q Patel, DJ Bulyk, ML Shi, Y Wang, Z |
| author_facet | Li, H Liefke, R Jiang, J Kurland, JV Tian, W Deng, P Zhang, W He, Q Patel, DJ Bulyk, ML Shi, Y Wang, Z |
| author_sort | Li, H |
| collection | OXFORD |
| description | The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression 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 components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. 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. |
| first_indexed | 2024-03-06T22:01:50Z |
| format | Journal article |
| id | oxford-uuid:4edba506-12af-4b73-bbd2-f49f30547c0f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:01:50Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:4edba506-12af-4b73-bbd2-f49f30547c0f2022-03-26T16:03:41ZPolycomb-like proteins link the PRC2 complex to CpG islandsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4edba506-12af-4b73-bbd2-f49f30547c0fEnglishSymplectic ElementsSpringer Nature2017Li, HLiefke, RJiang, JKurland, JVTian, WDeng, PZhang, WHe, QPatel, DJBulyk, MLShi, YWang, ZThe Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression 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 components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. 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. |
| spellingShingle | Li, H Liefke, R Jiang, J Kurland, JV Tian, W Deng, P Zhang, W He, Q Patel, DJ Bulyk, ML Shi, Y Wang, Z Polycomb-like proteins link the PRC2 complex to CpG islands |
| title | Polycomb-like proteins link the PRC2 complex to CpG islands |
| title_full | Polycomb-like proteins link the PRC2 complex to CpG islands |
| title_fullStr | Polycomb-like proteins link the PRC2 complex to CpG islands |
| title_full_unstemmed | Polycomb-like proteins link the PRC2 complex to CpG islands |
| title_short | Polycomb-like proteins link the PRC2 complex to CpG islands |
| title_sort | polycomb like proteins link the prc2 complex to cpg islands |
| work_keys_str_mv | AT lih polycomblikeproteinslinktheprc2complextocpgislands AT liefker polycomblikeproteinslinktheprc2complextocpgislands AT jiangj polycomblikeproteinslinktheprc2complextocpgislands AT kurlandjv polycomblikeproteinslinktheprc2complextocpgislands AT tianw polycomblikeproteinslinktheprc2complextocpgislands AT dengp polycomblikeproteinslinktheprc2complextocpgislands AT zhangw polycomblikeproteinslinktheprc2complextocpgislands AT heq polycomblikeproteinslinktheprc2complextocpgislands AT pateldj polycomblikeproteinslinktheprc2complextocpgislands AT bulykml polycomblikeproteinslinktheprc2complextocpgislands AT shiy polycomblikeproteinslinktheprc2complextocpgislands AT wangz polycomblikeproteinslinktheprc2complextocpgislands |