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  • PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis.

PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis.

Science advances (2020-06-05)
Yongqiang Hou, Wei Liu, Xianfu Yi, Yang Yang, Dongxue Su, Wei Huang, Hefen Yu, Xu Teng, Ying Yang, Wei Feng, Tao Zhang, Jie Gao, Kai Zhang, Rongfang Qiu, Yan Wang
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Histone Deacetylase 2 (HDAC2) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-Histone Deacetylase 1 (HDAC1) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-acetyl-Histone H3 (Lys27) Antibody, serum, Upstate®
Sigma-Aldrich
Anti-dimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-PHF20L1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, ab2
Sigma-Aldrich
Anti-RbAp48/RbAp46 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture
Sigma-Aldrich
Anti-monomethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit