Orchestration of H3K27 methylation: mechanisms and therapeutic implication

Pan, Mei-Ren; Hsu, Ming-Chuan; Chen, Li-Tzong; Hung, Wen‐Chun

doi:10.1007/s00018-017-2596-8

Cited by 68 publications

(58 citation statements)

References 147 publications

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“…Lysine residue 9 (H3K9) and lysine residue 27 (H3K27) of histone H3 were identified as transcription-repressive marks. Their methylation levels were associated with transcriptional repression and negative regulation of somatic reprogramming (Chen et al 2013, Mozzetta et al 2014, Cao et al 2015, Pan et al 2018. Aberrant H3K9 and H3K27 methylation levels were observed in pig SCNT embryos (Cao et al 2015, Huang et al 2016, Xie et al 2016.…”

Section: Introductionmentioning

confidence: 98%

“…Three categories of compounds commonly used for this purpose are DNA methyltransferase inhibitors (such as 5-aza-2′deoxyctidine) (Enright et al 2003), histone deacetylase inhibitors (such as trichostatin A and scriptaid) (Li et al 2008, Zhao et al 2009 and HMT inhibitors (such as BIX-01294 and GSK126) (Huang et al 2016, Xie et al 2016. Three-Deazaneplanocin A (DZNep) (Gannon et al 2013, Ostrup et al 2014 and UNC0642 (Liu et al 2013 are HMT inhibitors displaying excellent separation of functional potency and cell toxicity, thus suitable for cell-based and animal studies. DZNep and UNC0642 can cause selective reductions of H3K27me3 and H3K9me2, respectively.…”

Section: Introductionmentioning

confidence: 99%

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DZNep and UNC0642 enhance in vitro developmental competence of cloned pig embryos

et al. 2018

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Somatic cell nuclear transfer in mammalian cloning suffers from a faulty epigenetic reprogramming, which is believed to cause developmental failures in cloned embryos. Regulating the epigenetic-modifying enzymes can rescue the chromatin of cloned embryos from aberrant epigenetic status, thereby potentially promoting cloning efficiency. In this study, we investigated the effect of two histone methyltransferase inhibitors, namely, DZNep and UNC0642, on the in vitro developmental competence of cloned pig embryos. We found that (1) treatment with 10 nM DZNep or 5 nM UNC0642 for 24 h after activation had the best promoting effect on the development of cloned embryos (blastocyst rate 10.32% vs 18.08% for DZNep, and 10.44% vs 18.14% for UNC0642); (2) 10 nM DZNep and 5 nM UNC0642 significantly decreased the levels of H3K27me3 and H3K9me2, respectively, at the 2-cell, 4-cell and blastocyst stages; (3) the apoptosis level was lower in the treatment groups than in untreated control; and (4) the transcriptional expression of epigenetic genes (EZH2, GLP, G9a, Setdb1, Setdb2, Suv39h1 and Suv39h2) was decreased and pluripotency genes (Nanog, Pou5f1, Sox2 and Bmp4) was increased in treatment groups compared with control. These results indicated that treatment with DZNep and UNC0642 improves the epigenetic reprogramming of cloned embryos, which could render beneficial effect on the embryo quality and aberrant gene expression, and finally improve the developmental competence of cloned pig embryos.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

DZNep and UNC0642 enhance in vitro developmental competence of cloned pig embryos

et al. 2018

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“…EZH2 (enhancer of zeste homologue 2) is a human homologue of enhancer of zeste in drosophila and the key member of PcG [12,13], which is composed of PRC1 and PRC2 complexes [14]. EZH2 encodes the catalytic subunit of PRC2 and functions as a histone methyltransferase of H3K27 dimethylation and trimethylation [15] for silencing at specific genomic loci [16]. In ESCs, EZH2mediated H3K27me3 is necessary for cell identity and cell differentiation [17].…”

Section: Introductionmentioning

confidence: 99%

EZH2-mediated H3K27me3 inhibits ACE2 expression

Zhou

2020

Biochemical and Biophysical Research Communications

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Available online xxx Keywords: Coronavirus SARS-CoV-2 ACE2 EZH2 H3.3 a b s t r a c tThe outbreak of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is spreading globally and quickly, leading to emerging health issues. SARS-CoV-2 enters into and infects host cells through its spike glycoprotein recognizing the cell receptor Angiotensin-converting enzyme II (ACE2).Here, we noticed that ACE2 was further enhanced by SARS-CoV-2 infection. Human germ cells and early embryos express high level of ACE2. Notably, RNA-seq result showed that reduction of H3K27me3, but not H3K4/9/36me3, led to upregulation of Ace2 expression in mouse germ cell line GC-2. In agreement with this result, we found in human embryonic stem cells that ACE2 expression was significantly increased in absence of EZH2, the major enzyme catalyzing H3K27me3. ChIP-seq analysis further confirmed decrease of H3K27me3 signal and increase of H3K27ac signal at ACE2 promoter upon EZH2 knockout. Therefore, we propose that EZH2-mediated H3K27me3 at ACE2 promoter region inhibits ACE2 expression in mammalian cells. This regulatory pattern may also exist in other human cells and tissues. Our discovery provides clues for pathogenesis and targeted drug therapy towards ACE2 expression for prevention and adjuvant therapy of COVID-19.

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“…8d), we observed a difference in the accessibility of its target genes at the chromatin level. Indeed, we could measure enhanced trimethylation of H3K27, a marker of gene repression (Mondal et al , 2016; Pan et al , 2018), in adult plants (Fig. 9c), when considering promoters of representative ANAC017 target genes, identified among the juvenile-specific genes (Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential submergence tolerance between juvenile and adult Arabidopsis plants involves the ANAC017 transcription factor

Bui

Shukla

Giorgi

et al. 2020

Preprint

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Plants need to attune stress responses to the ongoing developmental programs to maximize their efficacy. For instance, successful submergence adaptation is often associated to a delicate poise between saving resources and their expenditure to activate measures that allow stress avoidance or attenuation. We observed a significant decrease in submergence tolerance associated with aging in Arabidopsis thaliana, with a critical step between two and three weeks of post-germination development. This sensitization to flooding was concomitant with the transition from juvenility to adulthood. Transcriptomic analyses indicated that a group of genes related to ABA and oxidative stress response was more expressed in juvenile plants than in adult ones. These genes are induced by endomembrane tethered ANAC factors that were in turn activated by submergence-associated oxidative stress. A combination of molecular, biochemical and genetic analyses showed that these genes are located in genomic regions that move towards a heterochromatic state with adulthood, as marked by lysine 4 dimethylation of histone H3. We concluded that, while the mechanism of flooding stress perception and signal transduction were unaltered between juvenile and adult phases, the sensitivity that these mechanisms set into action is integrated, via epigenetic regulation, into the developmental programme of the plant.

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Orchestration of H3K27 methylation: mechanisms and therapeutic implication

Cited by 68 publications

References 147 publications

DZNep and UNC0642 enhance in vitro developmental competence of cloned pig embryos

DZNep and UNC0642 enhance in vitro developmental competence of cloned pig embryos

EZH2-mediated H3K27me3 inhibits ACE2 expression

Differential submergence tolerance between juvenile and adult Arabidopsis plants involves the ANAC017 transcription factor

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