Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryza...Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryzae,histone H3K27 is found to associate with altered transcription of in planta induced genes.However,it is still unknown whether and how H3K27me3 modification is involved in pathogenicity to rice and stress response.In this study,we found that core subunits of PRC2,Kmt6-Suz12-Eed,were required for fungal pathogenicity to rice in M.oryzae.Kmt6-Suz12-Eed localized in the nuclei and was necessary for the establishment of H3K27me3 modification.With ChIP-seq analysis,9.0%of genome regions enriched with H3K27me3 occupancy,which corresponded to 1033 genes in M.oryzae.Furthermore,deletion of Kmt6,Suz12 or Eed altered genome-wide transcriptional expression,while the de-repression genes in theΔkmt6 strain were highly associated with H3K27me3 occupancy.Notably,plenty of genes which encode effectors and secreted enzymes,secondary metabolite synthesis genes,and cell wall stress-responsive genes were directly occupied with H3K27me3 modification and de-repression in theΔkmt6 strain.These results elaborately explained how PRC2 was required for pathogenicity,which is closely related to effector modulated host immunity and host environment adaption.展开更多
Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb rep...Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.展开更多
Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequ...Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.展开更多
Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
Polycomb Group Proteins(PcG)are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification.PcG proteins complex to form two types of epig...Polycomb Group Proteins(PcG)are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification.PcG proteins complex to form two types of epigenetic regulators:Polycomb Repressive Complex 1 and 2(PRC1 and PRC2).Although the mechanisms regulating PRC2 recruitment and activity in mammals remain poorly understood,recent work has identified a non-canonical PRC2 in mouse embryonic stem cells(mESC)with unique activities required for repression of PRC2 target genes and necessary for mESC differentiation and somatic cell reprogramming.Here we review the functions of PRC2 in embryonic stem cells and explore the role of the newly identified mESC specific PRC2 regulatory subunits Jarid2(jumonji,AT rich interactive domain 2),Mtf2(metal response element binding transcription factor 2)and esPRC2p48.展开更多
多聚梳抑制复合体2作为一种表观遗传调节因子可选择性催化组蛋白H3第27位赖氨酸三甲基化,从而诱导靶基因转录抑制。Zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)是多聚梳抑制复合体2中具有酶活性的亚基,在肿瘤触发、进展...多聚梳抑制复合体2作为一种表观遗传调节因子可选择性催化组蛋白H3第27位赖氨酸三甲基化,从而诱导靶基因转录抑制。Zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)是多聚梳抑制复合体2中具有酶活性的亚基,在肿瘤触发、进展、转移及耐药性方面有重要作用。EZH2与其他表观遗传修饰酶相互协调介导基因沉默,EZH2超表达是多种实体肿瘤晚期和转移性的标志,EZH2的表达与活性受多种肿瘤相关转录因子的调节,各位点氨基酸残基的磷酸化状态可影响EZH2的催化活性,EZH2基因突变在血液系统恶性肿瘤中频繁发生,除通过经典作用即催化抑癌基因启动子区组蛋白H3第27位赖氨酸甲基化来抑制转录外,EZH2还具有诱导基因活化功能。因此,EZH2成为肿瘤治疗的一个理想靶点,其特异性抑制剂EPZ6438正处于临床Ⅰ/Ⅱ期试验阶段。展开更多
Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were establish...Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were established by in-fection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. Results Western blot results showed that EZH2 protein level increased upon SIRT1 de-pletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter region of EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. Conclusions Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expres-sion.展开更多
Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as cr...Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.展开更多
The evolutionary conserved Polycomb Group(PcG)repressive system comprises two central protein complexes,PcG repressive complex 1(PRC1)and PRC2.These complexes,through the incorporation of histone modifications on chro...The evolutionary conserved Polycomb Group(PcG)repressive system comprises two central protein complexes,PcG repressive complex 1(PRC1)and PRC2.These complexes,through the incorporation of histone modifications on chromatin,have an essential role in the normal development of eukaryotes.In recent years,a significant effort has been made to characterize these complexes in the different kingdoms,and despite there being remarkable functional and mechanistic conservation,some key molecular principles have diverged.In this review,we discuss current views on the function of plant PcG complexes.We compare the composition of PcG complexes between animals and plants,highlight the role of recently identified plant PcG accessory proteins,and discuss newly revealed roles of known PcG partners.We also examine the mechanisms by which the repression is achieved and how these complexes are recruited to target genes.Finally,we consider the possible role of some plant PcG proteins in mediating local and long-range chromatin interactions and,thus,shaping chromatin 3D architecture.展开更多
基金the National Natural Science Foundation of China(Grant Nos.32170192 and 32000103)Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(Grant No.2021C02064)+1 种基金Key Research and Development Project of China National Rice Research Institute(Grant No.CNRRI-2020-04)the Chinese Academy of Agricultural Sciences under the‘Elite Youth’Program and the Agricultural Sciences and Technologies Innovation Program.
文摘Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryzae,histone H3K27 is found to associate with altered transcription of in planta induced genes.However,it is still unknown whether and how H3K27me3 modification is involved in pathogenicity to rice and stress response.In this study,we found that core subunits of PRC2,Kmt6-Suz12-Eed,were required for fungal pathogenicity to rice in M.oryzae.Kmt6-Suz12-Eed localized in the nuclei and was necessary for the establishment of H3K27me3 modification.With ChIP-seq analysis,9.0%of genome regions enriched with H3K27me3 occupancy,which corresponded to 1033 genes in M.oryzae.Furthermore,deletion of Kmt6,Suz12 or Eed altered genome-wide transcriptional expression,while the de-repression genes in theΔkmt6 strain were highly associated with H3K27me3 occupancy.Notably,plenty of genes which encode effectors and secreted enzymes,secondary metabolite synthesis genes,and cell wall stress-responsive genes were directly occupied with H3K27me3 modification and de-repression in theΔkmt6 strain.These results elaborately explained how PRC2 was required for pathogenicity,which is closely related to effector modulated host immunity and host environment adaption.
基金Project supported by the Fundamental Research Funds for the Central Universities from Lanzhou University (No.lzujbky-2014-87),China
文摘Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.
基金supported by the National Natural Science Foundation of China(32360166,31760321).
文摘Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
基金Hengbin Wang is a Sidney Kimmel Scholar and work in Wang Lab is supported by NIH Grant(GM081489).
文摘Polycomb Group Proteins(PcG)are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification.PcG proteins complex to form two types of epigenetic regulators:Polycomb Repressive Complex 1 and 2(PRC1 and PRC2).Although the mechanisms regulating PRC2 recruitment and activity in mammals remain poorly understood,recent work has identified a non-canonical PRC2 in mouse embryonic stem cells(mESC)with unique activities required for repression of PRC2 target genes and necessary for mESC differentiation and somatic cell reprogramming.Here we review the functions of PRC2 in embryonic stem cells and explore the role of the newly identified mESC specific PRC2 regulatory subunits Jarid2(jumonji,AT rich interactive domain 2),Mtf2(metal response element binding transcription factor 2)and esPRC2p48.
文摘多聚梳抑制复合体2作为一种表观遗传调节因子可选择性催化组蛋白H3第27位赖氨酸三甲基化,从而诱导靶基因转录抑制。Zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)是多聚梳抑制复合体2中具有酶活性的亚基,在肿瘤触发、进展、转移及耐药性方面有重要作用。EZH2与其他表观遗传修饰酶相互协调介导基因沉默,EZH2超表达是多种实体肿瘤晚期和转移性的标志,EZH2的表达与活性受多种肿瘤相关转录因子的调节,各位点氨基酸残基的磷酸化状态可影响EZH2的催化活性,EZH2基因突变在血液系统恶性肿瘤中频繁发生,除通过经典作用即催化抑癌基因启动子区组蛋白H3第27位赖氨酸甲基化来抑制转录外,EZH2还具有诱导基因活化功能。因此,EZH2成为肿瘤治疗的一个理想靶点,其特异性抑制剂EPZ6438正处于临床Ⅰ/Ⅱ期试验阶段。
基金Supported by National Natural Science Foundation of China (30721063)National Basic Research Program of China (973 Program) (2005CB522402, 2006CB910403)+1 种基金National Laboratory of Medical Molecular Biology grant (2060204)Beijing municipal government grant (YB20081002301)
文摘Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were established by in-fection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. Results Western blot results showed that EZH2 protein level increased upon SIRT1 de-pletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter region of EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. Conclusions Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expres-sion.
文摘Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.
基金This work was supported by a PID2019-106664GB-I00 grant from the Spanish Ministry of Science and Innovation.
文摘The evolutionary conserved Polycomb Group(PcG)repressive system comprises two central protein complexes,PcG repressive complex 1(PRC1)and PRC2.These complexes,through the incorporation of histone modifications on chromatin,have an essential role in the normal development of eukaryotes.In recent years,a significant effort has been made to characterize these complexes in the different kingdoms,and despite there being remarkable functional and mechanistic conservation,some key molecular principles have diverged.In this review,we discuss current views on the function of plant PcG complexes.We compare the composition of PcG complexes between animals and plants,highlight the role of recently identified plant PcG accessory proteins,and discuss newly revealed roles of known PcG partners.We also examine the mechanisms by which the repression is achieved and how these complexes are recruited to target genes.Finally,we consider the possible role of some plant PcG proteins in mediating local and long-range chromatin interactions and,thus,shaping chromatin 3D architecture.
