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
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
The maintenance of stem cells within the root meristem is the foundation for the continuous growth of the root system.The PLETHORA(PLT)transcription factors control root meristem patterning,but the underlying molecula...The maintenance of stem cells within the root meristem is the foundation for the continuous growth of the root system.The PLETHORA(PLT)transcription factors control root meristem patterning,but the underlying molecular mechanism remains unclear.In this study,we show that rice PLT3,PLT4,and PLT5 promote a repressive chromatin state to maintain stem cell fate in the root meristem.We demonstrated that PLT5 interacts with Polycomb repressive complex 2(PRC2),which deposits the repressive mark H3K27me3,and the histone demethylase JMJ703,which removes the active mark H3K4me3 in rice root meristem cells.In addition,JMJ703 itself associates with PRC2 proteins.We found that loss of PLT3,PLT4,and PLT5 function results in decreased PRC2 association H3K27me3,increased H3K4me3,and upregulated expression of genes decorated with the two marks in the root meristem.Further analyses revealed that PLT interactions with PRC2 and JMJ703 enhance the H3K27me3/H3K4me3 ratio at a set of bivalent genes,thereby maintaining their silent state.Taken together,these results uncover a chromatin mechanism by which PLTs control the stem cell fate in the rice root meristem.展开更多
Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer develop...Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.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.
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.
基金supported by National Natural Science Foundation of China(324700359 and 32470307)the Fundamental Research Funds for the Central Universities,China(2016RC003,2662025SKPY002,and 2662015PY228)+2 种基金the Fundamental Research Program of Hubei Province(2024AFE001)the Earmarked Fund for China Agriculture Research System(No.CARS-01)Fujian Provincial Middle-aged and Young Teachers Education Research Project(JAT241023).
文摘The maintenance of stem cells within the root meristem is the foundation for the continuous growth of the root system.The PLETHORA(PLT)transcription factors control root meristem patterning,but the underlying molecular mechanism remains unclear.In this study,we show that rice PLT3,PLT4,and PLT5 promote a repressive chromatin state to maintain stem cell fate in the root meristem.We demonstrated that PLT5 interacts with Polycomb repressive complex 2(PRC2),which deposits the repressive mark H3K27me3,and the histone demethylase JMJ703,which removes the active mark H3K4me3 in rice root meristem cells.In addition,JMJ703 itself associates with PRC2 proteins.We found that loss of PLT3,PLT4,and PLT5 function results in decreased PRC2 association H3K27me3,increased H3K4me3,and upregulated expression of genes decorated with the two marks in the root meristem.Further analyses revealed that PLT interactions with PRC2 and JMJ703 enhance the H3K27me3/H3K4me3 ratio at a set of bivalent genes,thereby maintaining their silent state.Taken together,these results uncover a chromatin mechanism by which PLTs control the stem cell fate in the rice root meristem.
基金supported by the National Key R&D Program of China(2016YFE0129200)the National Natural Science Foundation of China(31571321,31171428)the Institute of the Fundamental Research Funds of Shandong University(2015JC036)
文摘Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.
