Towards understanding of PRC2 binding to RNA

Yan, Junli; Dutta, Bibek; Hee, Yan Ting; Chng, Wee‐Joo

doi:10.1080/15476286.2019.1565283

Cited by 43 publications

(35 citation statements)

References 88 publications

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“…These results suggest that Ppp1r1b-lncRNA physically associates with PRC2 complex at promoters of myogenic transcription factors. The inhibition of H3K27me3 by Ppp1r1b-lncRNA could be due to inhibition of PRC2 activity or eviction of PRC2 from chromatin by Ppp1r1b-lncRNA (Yan et al 2019). It was also proposed that PRC2 recruitment or eviction is determined by the rate at which RNA is released from the locus.…”

Section: Discussionmentioning

confidence: 99%

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human

Kang

Zhao

Arsdell

et al. 2020

RNA

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Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators and play important roles in cardiac development and congenital heart disease. In a previous study, we identified a novel lncRNA, Ppp1r1b, with expression highly correlated with myogenesis. However, the molecular mechanism that underlies Ppp1r1b-lncRNA function in myogenic regulation is unknown. By silencing Ppp1r1b-lncRNA, mouse C2C12 and human skeletal myoblasts failed to develop fully differentiated myotubes. Myogenic differentiation was also impaired in PPP1R1B-lncRNA deficient human-induced pluripotent stem cell-derived cardiomyocytes (hiPSCs-CMs). The expression of myogenic transcription factors, including MyoD, Myogenin, and Tbx5, as well as sarcomere proteins, was significantly suppressed in Ppp1r1b-lncRNA inhibited myoblast cells and neonatal mouse heart. Histone modification analysis revealed increased H3K27 tri-methylation at MyoD1 and Myogenin promoters in GapmeR treated C2C12 cells. Furthermore, Ppp1r1b-lncRNA was found to bind to Ezh2, and chromatin isolation by RNA purification (ChIRP) assay revealed enriched interaction of Ppp1r1b-lncRNA with Myod1 and Tbx5 promoters, suggesting that Ppp1r1b-lncRNA induces transcription of myogenic transcription factors by interacting with the polycomb repressive complex 2 (PRC2) at the chromatin interface. Correspondingly, the silencing of Ppp1r1b-lncRNA increased EZH2 binding at promoter regions of myogenic transcription factors. Therefore, our results suggest that Ppp1r1b-lncRNA promotes myogenic differentiation through competing for PRC2 binding with chromatin of myogenic master regulators during heart and skeletal muscle development.

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Section: Discussionmentioning

confidence: 99%

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human

Kang

Zhao

Arsdell

et al. 2020

RNA

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“…For example, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, can promote DNA methylation by recruiting DNMTs in the target promoter region and then result in gene silencing [ 42 ]. Besides, lncRNAs regulate gene expression through interaction with histone modification enzymes, DNA methyltransferases [ 43 , 44 ], or miRNA [ 45 ]. For example, some lncRNAs such as ANRIL are reported to regulate gene expression by recruiting the polycomb group of proteins, which can lead to heritable gene silencing through di- or trimethylation of lysine 27 of histone 3 (H3K27me2/3) [ 43 , 44 , 46 ].…”

Section: Epigeneticsmentioning

confidence: 99%

“…Besides, lncRNAs regulate gene expression through interaction with histone modification enzymes, DNA methyltransferases [ 43 , 44 ], or miRNA [ 45 ]. For example, some lncRNAs such as ANRIL are reported to regulate gene expression by recruiting the polycomb group of proteins, which can lead to heritable gene silencing through di- or trimethylation of lysine 27 of histone 3 (H3K27me2/3) [ 43 , 44 , 46 ]. In addition, lncRNAs can regulate the repression activity of miRNAs on mRNA [ 47 ].…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetic Regulation of Dental Pulp Stem Cell Fate

Zhou

Gan

Yan

et al. 2020

Stem Cells International

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Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

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“…This elucidates to the extensive effects of PRC2 on transcriptional regulation of target genes and institutes it as an essential complex to gather further understandings. It is worth noting that quite comprehensive reviews on molecular mechanisms of PRC2 recruitment and function, interactions in the PRC2 complex assembly and spreading of local H3K27me3, and interactions of PRC2 with RNA were recently published.…”

Section: Introductionmentioning

confidence: 99%

Polycomb repressive 2 complex—Molecular mechanisms of function

Kouznetsova

Tchekanov

Li³

et al. 2019

Protein Science

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Numerous molecular processes conduct epigenetic regulation of protein transcription to maintain cell specification. In this review, we discuss molecular mechanisms of the Polycomb group of proteins and its enzymatic role in epigenetics. More specifically, we focus on the Polycomb repressive complex 2 (PRC2) and the effects of its repressive marker. We have compiled information regarding the biological structure and how that impacts the stability of the complex. In addition, we examined functions of the individual core proteins of PRC2 in relation to the accessory proteins that interact with the complex. Lastly, we discuss the implications of unregulated and downregulated PRC2 activity in Alzheimer's disease and cancer and possible methods of treatment related to PRC2 regulation.

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Towards understanding of PRC2 binding to RNA

Cited by 43 publications

References 88 publications

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human

Epigenetic Regulation of Dental Pulp Stem Cell Fate

Polycomb repressive 2 complex—Molecular mechanisms of function

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