PRC2 regulates RNA polymerase III transcribed non-translated RNA gene transcription through EZH2 and SUZ12 interaction with TFIIIC complex.

Chang Liu,Hongquan Zhang,Hao Jiang,Junhu Wan,Zhaoli Liu,Xiaoyan Dai,Ji Ma,Peng Wang,Shuai Li

doi:10.1093/nar/gkv574

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 tRNATyr, 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.

Highlights

Polycomb group proteins are important epigenetic regulators that play crucial roles in embryonic development and differentiation [1,2]
In the present report we uncovered a novel role of EZH2, as a key epigenetic regulator, in controlling transcription of a subset of small RNA genes transcribed by RNA polymerase III including transfer RNA (tRNA), 5S rRNA and 7SL RNA
For the first time we identified that EZH2 is linked with RNA polymerase III transcription by demonstrating its interaction with members of a transcriptional factor complex, transcriptional factor complex IIIC (TFIIIC)

Summary

Introduction

Polycomb group proteins are important epigenetic regulators that play crucial roles in embryonic development and differentiation [1,2]. EZH2 (Enhancer of Zeste Homolog 2) is a member of polycomb protein family, which forms. EZH2 is the core catalytic component of PRC2, mediating trimethylation of histone H3 at lysine 27 (H3K27) through the SET domain, repressing the transcription of target genes [6,7]. It was found that phosphorylated EZH2 was able to activate STAT3 signaling through increased tyrosine phosphorylation of STAT3 via direct methylation of it, EZH2 could regulate gene transcription by integrating with estrogen and Wnt signaling as a coactivator [8,9]. The oncogenic role of EZH2 in castrationresistant prostate cancer was found independent of PRC2 complex [10]

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