A Class of Protein-Coding RNAs Binds to Polycomb Repressive Complex 2 and Alters Histone Methylation

Meijian Liao,Shoucui Gao,Yaou Zhang,Xiaolin Sun

doi:10.3389/fonc.2021.739830

Abstract

Polycomb repressive complex 2 (PRC2) is a multi-subunit protein complex mediating the methylation of lysine 27 on histone H3 and playing an important role in transcriptional repression during tumorigenesis and development. Previous studies revealed that both protein-coding and non-coding RNAs could bind to PRC2 complex. However, the functions of protein-coding RNAs that bind to PRC2 complex in tumor are still unknown. Through data mining and RNA immunoprecipitation (RIP) assay, our study found that there were a class of protein-coding RNAs bound to PRC2 complex and H3 with tri-methylation on lysine 27. The Bayesian gene regulatory network analysis pointed out that these RNAs regulated the expression of PRC2-regulated genes in cancer. In addition, gene set enrichment analysis (GSEA), gene ontology (GO) analysis, and weighted gene co-expression network analysis (WGCNA) also confirmed that these RNAs were associated with histone modification in cancer. We also confirmed that MYO1C, a PRC2-bound transcript, inhibited the modification level of H3K27me3. Further detailed study showed that TMEM117 regulated TSLP expression through EZH2-mediated H3K27me3 modification. Interestingly, the RNA recognition motif of PRC2 complex might help these RNAs bind to the PRC2 complex more easily. The same regulatory pattern was found in mice as well.

Highlights

Tri-methylation of the H3 histone at Lys 27 (H3K27me3) is critical for long-term transcriptional repression, playing an important role during tumorigenesis and development [1]
We show that there is a class of protein-coding RNAs that binds to polycomb repressive complex 2 (PRC2) complex and epigenetically regulates gene expression
The fragments of RNAs that bound to EZH2 and SUZ12 proteins were analyzed in the fRIP-seq data of EZH2 and SUZ12 (GSE67963) using the annotatePeak function of ChIPseeker package of R language [34]

Summary

Introduction

Tri-methylation of the H3 histone at Lys 27 (H3K27me3) is critical for long-term transcriptional repression, playing an important role during tumorigenesis and development [1]. The modification of H3K27me catalyzed by the polycomb repressive complex 2 (PRC2) is well studied. PRC2 complex contains three major proteins: EZH2, SUZ12, and EED. The EZH2 catalytic subunit, a methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 leading to the epigenetic repression of its target gene [2]. SUZ12 protein acts as stability factor for PRC2 complex and influences the catalytic activity of EZH2 [3]. EED protein can bind to histone with an H3K27me

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Results

Conclusion