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
The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Pol...The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Polycomb Repressive Complex 1(PRC1), PRC2, and Polycomb Repressive De UBiquitinase(PR-DUB).Their deregulation has been associated with human cancer initiation and progression. Here we review the updated understanding for Pc G proteins in transcription regulation and DNA damage repair and highlight increasing links to the hallmarks in cancer. Accordingly, we discuss some of the recent advances in drug development or strategies against cancers caused by the gain or loss of PcG functions.展开更多
The Polycomb group （PcG） genes repress gene expression mainly through chromatin modifications and regulation of chromatin structure. At present, at/east four protein complexes of PcG proteins are identified, includi...The Polycomb group （PcG） genes repress gene expression mainly through chromatin modifications and regulation of chromatin structure. At present, at/east four protein complexes of PcG proteins are identified, including Polycomb repressive complex 1 （PRC1）, Polycomb repressive complex 2 （PRC2）, PHO-repressive complex （PhoRC） and Polycomb repressive deubiquitinase （PR-DUB）. In this review, the recent discoveries of the composition of the above complexes, as well as their roles in regulating histone modifications and gene silencing are discussed. We mainly focus on the composition of PRC1 and PRC2 complex and recruitment of PcG to target genes and mechanisms of PRC1 and PRC2-mediated gene silencing. Although much progress has been made in understanding gene silencing mediated by PcG proteins, we also discuss several important questions that still remained unanswered, such as the inheritance of histone modifications during cell division.展开更多
Polycomb group（PcG） proteins are crucial epigenetic regulators conferring transcriptional memory to cell lineages.They assemble into multi-protein complexes,e.g.,Polycomb Repressive Complex 1 and 2（PRC1,PRC2）,whic...Polycomb group（PcG） proteins are crucial epigenetic regulators conferring transcriptional memory to cell lineages.They assemble into multi-protein complexes,e.g.,Polycomb Repressive Complex 1 and 2（PRC1,PRC2）,which are thought to act in a sequential manner to stably maintain gene repression.PRC2 induces histone H3 lysine 27（H3K27） trimethylation（H3K27me3）,which is subsequently read by PRCl that further catalyzes H2A monoubiquitination（H2Aub1）,creating a transcriptional silent chromatin conformation.PRC2 components are conserved in plants and have been extensively characterized in Arabidopsis.In contrast,PRCl composition and function are more diverged between animals and plants.Only more recently,PRC1 existence in plants has been documented.Here we review the aspects of plant specific and conserved PRC1 and highlight critical roles of PRC1 components in seed embryonic trait determinacy,shoot stem cell fate determinacy,and flower development in Arabidopsis.展开更多
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
Objective To study the regulatory mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1. Methods HeLa epithelial cells were treated with either histone...Objective To study the regulatory mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1. Methods HeLa epithelial cells were treated with either histone deacetylase inhibitor (HDACi) trichostatin A (TSA) or DNA methylation inhibitor 5-Aza-C before detecting SATB1 expression. Luciferase reporter system was applied to measure effects of EZH2 on SATB1 promoter activity. Over-expression or knockdown of EZH2 and subsequent quantitative reverse transcription-polymerase chain reaction were performed to determine the effect of this Polycomb group protein on SATB1 transcription. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of EZH2 and trimethylated H3K27 (H3K27me3) at SATB1 promoter in HeLa cells. K562 cells and Jurkat cells, both having high-level expression of SATB1, were used in the ChIP experiment as controls. Results Both TSA and 5-Aza-C increased SATB1 expression in HeLa cells. Over-expression of EZH2 reduced promoter activity as well as the mRNA level of SATB1, while knockdown of EZH2 apparently enhanced SATB1 expression in HeLa cells but not in K562 cells and Jurkat cells. ChIP assay results suggested that epigenetic silencing of SATB1 by EZH2 in HeLa cells was mediated by trimethylation modification of H3K27. In contrast, enrichment of EZH2 and H3K27me3 was not detected within proximal promoter region of SATB1 in either K562 or Jurkat cells. Conclusion SATB1 is a bona fide EZH2 target gene in HeLa cells and the repression of SATB1 by EZH2 may be mediated by trimethylation modification on H3K27.展开更多
The Polycomb group protein Bmi1 is a constituent of the Polycomb repressive complex 1, and it is an important molecule for the regulation of the self-renewal of hematopoietic stem cells. In the field of clinical hemat...The Polycomb group protein Bmi1 is a constituent of the Polycomb repressive complex 1, and it is an important molecule for the regulation of the self-renewal of hematopoietic stem cells. In the field of clinical hematology, there are reports that the level of Bmi1 expression in blast cells is related to the prognosis of acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. We investigated whether the level of Bmi1 expression in leukemic cells is related to the prognosis and the characteristics of childhood acute lymphoblastic leukemia. In all the leukemic blast cells, Bmi1 gene expression was lower value than that in normal B cells. There were no correlations between the level of Bmi1 gene expression in leukemic blast cells and other parameters, including prognosis. Here, we report that the level of Bmi1 expression in blast cells is not related to the prognosis of pediatric acute lymphoblastic leukemia.展开更多
The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in...The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31;Smarca1/?17;Dnmt3b/4.7;Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.展开更多
Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
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
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 Key Research and Development Program (2017YFA0504102)the National Natural Science Foundation of China (81772676, 31970579)+3 种基金the Natural Science Foundation of Tianjin Municipal Science and Technology Commission (18JCJQJC48200)Key Research Project of Tianjin Education Commission (2020ZD13)Open grant from the Chinese Academy of Medical Sciences (157-Zk19-02 and Z20-04)the Talent Excellence Program from Tianjin Medical University and Research Project of Tianjin Education Commission。
文摘The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Polycomb Repressive Complex 1(PRC1), PRC2, and Polycomb Repressive De UBiquitinase(PR-DUB).Their deregulation has been associated with human cancer initiation and progression. Here we review the updated understanding for Pc G proteins in transcription regulation and DNA damage repair and highlight increasing links to the hallmarks in cancer. Accordingly, we discuss some of the recent advances in drug development or strategies against cancers caused by the gain or loss of PcG functions.
基金Supported by the National Key Basic Research Program of China(973 Program)(2011CB504206,2012CB518700)the National Natural Science Foundation of China(91019013,31221061,31200653 and 31370866)Program for New Century Excellent Talents in University(NCET-11-0410)
文摘The Polycomb group （PcG） genes repress gene expression mainly through chromatin modifications and regulation of chromatin structure. At present, at/east four protein complexes of PcG proteins are identified, including Polycomb repressive complex 1 （PRC1）, Polycomb repressive complex 2 （PRC2）, PHO-repressive complex （PhoRC） and Polycomb repressive deubiquitinase （PR-DUB）. In this review, the recent discoveries of the composition of the above complexes, as well as their roles in regulating histone modifications and gene silencing are discussed. We mainly focus on the composition of PRC1 and PRC2 complex and recruitment of PcG to target genes and mechanisms of PRC1 and PRC2-mediated gene silencing. Although much progress has been made in understanding gene silencing mediated by PcG proteins, we also discuss several important questions that still remained unanswered, such as the inheritance of histone modifications during cell division.
基金supported by the French Centre National de la Recherche Scientifique(CNRS)the French Agence Nationale de la Recherche(ANR-08-BLAN- 0200-CSD7)
文摘Polycomb group（PcG） proteins are crucial epigenetic regulators conferring transcriptional memory to cell lineages.They assemble into multi-protein complexes,e.g.,Polycomb Repressive Complex 1 and 2（PRC1,PRC2）,which are thought to act in a sequential manner to stably maintain gene repression.PRC2 induces histone H3 lysine 27（H3K27） trimethylation（H3K27me3）,which is subsequently read by PRCl that further catalyzes H2A monoubiquitination（H2Aub1）,creating a transcriptional silent chromatin conformation.PRC2 components are conserved in plants and have been extensively characterized in Arabidopsis.In contrast,PRCl composition and function are more diverged between animals and plants.Only more recently,PRC1 existence in plants has been documented.Here we review the aspects of plant specific and conserved PRC1 and highlight critical roles of PRC1 components in seed embryonic trait determinacy,shoot stem cell fate determinacy,and flower development in Arabidopsis.
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 mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1. Methods HeLa epithelial cells were treated with either histone deacetylase inhibitor (HDACi) trichostatin A (TSA) or DNA methylation inhibitor 5-Aza-C before detecting SATB1 expression. Luciferase reporter system was applied to measure effects of EZH2 on SATB1 promoter activity. Over-expression or knockdown of EZH2 and subsequent quantitative reverse transcription-polymerase chain reaction were performed to determine the effect of this Polycomb group protein on SATB1 transcription. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of EZH2 and trimethylated H3K27 (H3K27me3) at SATB1 promoter in HeLa cells. K562 cells and Jurkat cells, both having high-level expression of SATB1, were used in the ChIP experiment as controls. Results Both TSA and 5-Aza-C increased SATB1 expression in HeLa cells. Over-expression of EZH2 reduced promoter activity as well as the mRNA level of SATB1, while knockdown of EZH2 apparently enhanced SATB1 expression in HeLa cells but not in K562 cells and Jurkat cells. ChIP assay results suggested that epigenetic silencing of SATB1 by EZH2 in HeLa cells was mediated by trimethylation modification of H3K27. In contrast, enrichment of EZH2 and H3K27me3 was not detected within proximal promoter region of SATB1 in either K562 or Jurkat cells. Conclusion SATB1 is a bona fide EZH2 target gene in HeLa cells and the repression of SATB1 by EZH2 may be mediated by trimethylation modification on H3K27.
文摘The Polycomb group protein Bmi1 is a constituent of the Polycomb repressive complex 1, and it is an important molecule for the regulation of the self-renewal of hematopoietic stem cells. In the field of clinical hematology, there are reports that the level of Bmi1 expression in blast cells is related to the prognosis of acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. We investigated whether the level of Bmi1 expression in leukemic cells is related to the prognosis and the characteristics of childhood acute lymphoblastic leukemia. In all the leukemic blast cells, Bmi1 gene expression was lower value than that in normal B cells. There were no correlations between the level of Bmi1 gene expression in leukemic blast cells and other parameters, including prognosis. Here, we report that the level of Bmi1 expression in blast cells is not related to the prognosis of pediatric acute lymphoblastic leukemia.
文摘The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31;Smarca1/?17;Dnmt3b/4.7;Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.
文摘Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
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.
