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PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis
TUDOR domain–containing proteins (TDRDs) are chiefly responsible for recognizing methyl-lysine/arginine residue. However, how TDRD dysregulation contributes to breast tumorigenesis is poorly understood. Here, we report that TUDOR domain–containing PHF20L1 as a H3K27me2 reader exerts transcriptional...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159910/ https://www.ncbi.nlm.nih.gov/pubmed/32494608 http://dx.doi.org/10.1126/sciadv.aaz0356 |
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author | Hou, Yongqiang Liu, Wei Yi, Xianfu Yang, Yang Su, Dongxue Huang, Wei Yu, Hefen Teng, Xu Yang, Ying Feng, Wei Zhang, Tao Gao, Jie Zhang, Kai Qiu, Rongfang Wang, Yan |
author_facet | Hou, Yongqiang Liu, Wei Yi, Xianfu Yang, Yang Su, Dongxue Huang, Wei Yu, Hefen Teng, Xu Yang, Ying Feng, Wei Zhang, Tao Gao, Jie Zhang, Kai Qiu, Rongfang Wang, Yan |
author_sort | Hou, Yongqiang |
collection | PubMed |
description | TUDOR domain–containing proteins (TDRDs) are chiefly responsible for recognizing methyl-lysine/arginine residue. However, how TDRD dysregulation contributes to breast tumorigenesis is poorly understood. Here, we report that TUDOR domain–containing PHF20L1 as a H3K27me2 reader exerts transcriptional repression by recruiting polycomb repressive complex 2 (PRC2) and Mi-2/nucleosome remodeling and deacetylase (NuRD) complex, linking PRC2-mediated methylation and NuRD-mediated deacetylation of H3K27. Furthermore, PHF20L1 was found to serve as a potential MYC and hypoxia-driven oncogene, promoting glycolysis, proliferation, and metastasis of breast cancer cells by directly inhibiting tumor suppressors such as HIC1, KISS1, and BRCA1. PHF20L1 expression was also strongly correlated with higher histologic grades of breast cancer and markedly up-regulated in several cancers. Meanwhile, Phf20l1 deletion not only induces growth retardation and mammary ductal outgrowth delay but also inhibits tumorigenesis in vivo. Our data indicate that PHF20L1 promotes tumorigenesis, supporting the pursuit of PHF20L1 as a target for cancer therapy. |
format | Online Article Text |
id | pubmed-7159910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71599102020-06-02 PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis Hou, Yongqiang Liu, Wei Yi, Xianfu Yang, Yang Su, Dongxue Huang, Wei Yu, Hefen Teng, Xu Yang, Ying Feng, Wei Zhang, Tao Gao, Jie Zhang, Kai Qiu, Rongfang Wang, Yan Sci Adv Research Articles TUDOR domain–containing proteins (TDRDs) are chiefly responsible for recognizing methyl-lysine/arginine residue. However, how TDRD dysregulation contributes to breast tumorigenesis is poorly understood. Here, we report that TUDOR domain–containing PHF20L1 as a H3K27me2 reader exerts transcriptional repression by recruiting polycomb repressive complex 2 (PRC2) and Mi-2/nucleosome remodeling and deacetylase (NuRD) complex, linking PRC2-mediated methylation and NuRD-mediated deacetylation of H3K27. Furthermore, PHF20L1 was found to serve as a potential MYC and hypoxia-driven oncogene, promoting glycolysis, proliferation, and metastasis of breast cancer cells by directly inhibiting tumor suppressors such as HIC1, KISS1, and BRCA1. PHF20L1 expression was also strongly correlated with higher histologic grades of breast cancer and markedly up-regulated in several cancers. Meanwhile, Phf20l1 deletion not only induces growth retardation and mammary ductal outgrowth delay but also inhibits tumorigenesis in vivo. Our data indicate that PHF20L1 promotes tumorigenesis, supporting the pursuit of PHF20L1 as a target for cancer therapy. American Association for the Advancement of Science 2020-04-15 /pmc/articles/PMC7159910/ /pubmed/32494608 http://dx.doi.org/10.1126/sciadv.aaz0356 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Hou, Yongqiang Liu, Wei Yi, Xianfu Yang, Yang Su, Dongxue Huang, Wei Yu, Hefen Teng, Xu Yang, Ying Feng, Wei Zhang, Tao Gao, Jie Zhang, Kai Qiu, Rongfang Wang, Yan PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title | PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title_full | PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title_fullStr | PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title_full_unstemmed | PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title_short | PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
title_sort | phf20l1 as a h3k27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159910/ https://www.ncbi.nlm.nih.gov/pubmed/32494608 http://dx.doi.org/10.1126/sciadv.aaz0356 |
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