title: PRC2 regulates RNA polymerase III transcribed non-translated RNA gene transcription through EZH2 and SUZ12 interaction with TFIIIC complex.
abstract: Polycomb repression complex 2 (PRC2) component EZH2 tri-methylates H3K27 and exerts epigenetic repression on target gene expression. EZH2-mediated epigenetic control of RNA polymerase II (Pol II) transcribed coding gene transcription has been well established. However, little is known about EZH2-mediated epigenetic regulation of RNA polymerase III (Pol III) transcription. Here we present a paradigm that EZH2 is involved in the repression of Pol III transcription via interaction with transcriptional factor complex IIIC (TFIIIC). EZH2 and H3K27me3 co-occupy the promoter of tRNA(Tyr), 5S rRNA and 7SL RNA genes. Depletion of EZH2 or inhibition of EZH2 methyltransferase activity led to upregulation of Pol III target gene transcription. EZH2-mediated repression of Pol III transcribed gene expression requires presence of SUZ12. SUZ12 was able to interact with TFIIIC complex and knockdown of SUZ12 decreased occupancy of EZH2 and H3K27me3 at the promoter of Pol III target genes. Our findings pointed out a previously unidentified role of PRC2 complex in suppressing transcription of Pol III transcribed non-translated RNA genes, putting Pol III on a new layer of epigenetic regulation.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Junhu
authors.initials: J
authors.lastname: Wan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xue Yuan Road, Beijing 100191, China Hongquan.Zhang@bjmu.edu.cn.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012320:RNA Polymerase III / Q000378:metabolism*; D012341:RNA, Ribosomal, 5S / Q000235:genetics; D020733:RNA, Small Cytoplasmic / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D018271:Signal Recognition Particle / Q000235:genetics; D014157:Transcription Factors; D019474:Transcription Factors, TFIII / Q000378:metabolism*; D014158:Transcription, Genetic; D000098832:Transcription Factor TFIIIC
chemical_list: C115990:7SL RNA; C463859:GTF3C3 protein, human; D006657:Histones; D009363:Neoplasm Proteins; D012341:RNA, Ribosomal, 5S; D020733:RNA, Small Cytoplasmic; C430461:SUZ12 protein, human; D018271:Signal Recognition Particle; D014157:Transcription Factors; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC; D012343:RNA, Transfer; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D012320:RNA Polymerase III