Coupling of H3K27me3 recognition with transcriptional repression through the BAH-PHD-CPL2 complex in Arabidopsis

Yi-Zhe Zhang,Li Peng,Cheng-Guo Duan,Si-Si Xie,Jianlong Yuan,Lingrui Zhang,Jing Jiang,Yuhua Wang,Jian-Kang Zhu,Chunxiang Chen,Guiping Zhang,Jiamu Du

doi:10.1038/s41467-020-20089-0

Abstract

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis. The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 (AGO5). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing.

Highlights

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes
Through a mass spectrometry (MS) analysis of the chromatin regulator antisilencing 1 (ASI1), we previously demonstrated that BAH domain-containing protein AIPP3, and PHD protein AIPP2 and CPL2 are associated with ASI1
This association was further confirmed by immunoprecipitation assays coupled to a mass spectrometry analysis (IP–MS) of AIPP3, AIPP2, and CPL2 in which AIPP3, AIPP2, and CPL2 could be mutually co-purified with one another except for ASI1 (Fig. 1a and Supplementary Data 1)

Summary

Introduction

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. Three major models have been proposed to explain the mechanisms of PRC complex-mediated transcription repression[8] For those bivalent promoters marked by both H3K27me[3] and H3K4me[3] marks, PcG complexes are believed to hold the poised Pol II at the transcription start site (TSS), resulting in the inhibition of Pol II release. (AIPP3) and two PHD domain-containing proteins AIPP2/ PARALOG OF AIPP2 (PAIPP2) could form a BAH–PHD module to read H3K27me[3] and unmethylated H3K4, respectively, and coordinate in implementing transcriptional repression of hundreds of genes, those development and stressresponsive genes in Arabidopsis, such as the florigen gene FT and the RNA silencing effector gene AGO5. Our findings reveal a coupling of the H3K27me[3] recognition and downstream transcriptional repression through the BPC complex This pathway may represent a mechanism of H3K27me3-mediated gene silencing

Methods

Results

Conclusion