In the cell nucleus,DNA is wound around histone proteins,which are then packed together to form chromatin.Histones can be chemically tagged by methyl and acetyl groups.Polycomb group (PcG) proteins attach methyl group...In the cell nucleus,DNA is wound around histone proteins,which are then packed together to form chromatin.Histones can be chemically tagged by methyl and acetyl groups.Polycomb group (PcG) proteins attach methyl groups to genes,which block their activity.This is similar to the attachment of methyl groups to gene promoters by DNA methyltransferases (DNMTs).This action is directly linked with tumor initiation and metastasis via the promotion of anti-senescence and anti-apoptosis pathways,and by facilitating epithelial mesenchymal transition (EMT).Cell fate transcriptional factors (CFTFs) and long non-coding RNAs (long ncRNAs) recruit PcG proteins to the promoters of tumor suppressor genes,resulting in epigenetic gene silencing by influencing chromatin structure and DNA accessibility.Thus,PcG proteins are potential diagnostic markers and targets for new chemoprevention and therapeutic strategies.展开更多
The developmental program of seeds is promoted by master regulators that are expressed in a seed-specific manner. Ectopic expression studies reveal that expression of these master regulators and other transcriptional ...The developmental program of seeds is promoted by master regulators that are expressed in a seed-specific manner. Ectopic expression studies reveal that expression of these master regulators and other transcriptional regulators is sufficient to promote seed-associated traits, including generation of somatic embryos. Recent work highlights the importance of chromatin-associated factors in restricting expression of seed-specific genes, in particular PcG proteins and ATP-dependent remodelers. This review summarizes what is known regarding factors that promote zygotic and/or somatic embryogenesis and the chromatin machinery that represses their expression. Characterization of the regulation of seedspecific genes reveals that plant chromatin-based repression systems exhibit broad conservation with and surprising differences from animal repression systems.展开更多
Recently, it has been shown that plants contain homologs to the animal Polycomb repressive complex I （PRC1） components BM11 and RINGIA/B. In Arabidopsis, there are three BMIl-like genes, two of which, AtBMIIA and B,...Recently, it has been shown that plants contain homologs to the animal Polycomb repressive complex I （PRC1） components BM11 and RINGIA/B. In Arabidopsis, there are three BMIl-like genes, two of which, AtBMIIA and B, are required during post-embryonic plant growth to repress embryonic traits and allow cell differentiation. However, little is known about the third BMIl-like gene, AtBMIIC. In this work, we show that AtBMIIC is only expressed during endosperm and stamen development. AtBMIIC is an imprinted gene expressed from the maternal allele in the endosperm but bialleli- cally expressed in stamen. We found that the characteristic expression pattern of AtBMIIC is the result of a complex epigenetic regulation that involves CG DNA methylation, RNA-directed non-CG DNA methylation （RdDM）, and PcG activity. Our results show the orchestrated interplay of different epigenetic mechanisms in regulating gene expression throughout development, shedding light on the current hypotheses for the origin and mechanism of imprinting in plant endosperm.展开更多
Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and i...Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.展开更多
基金supported by the National Basic Research Program of China(2011CB504300)the National Natural Science Foundation of China(30930101)
文摘In the cell nucleus,DNA is wound around histone proteins,which are then packed together to form chromatin.Histones can be chemically tagged by methyl and acetyl groups.Polycomb group (PcG) proteins attach methyl groups to genes,which block their activity.This is similar to the attachment of methyl groups to gene promoters by DNA methyltransferases (DNMTs).This action is directly linked with tumor initiation and metastasis via the promotion of anti-senescence and anti-apoptosis pathways,and by facilitating epithelial mesenchymal transition (EMT).Cell fate transcriptional factors (CFTFs) and long non-coding RNAs (long ncRNAs) recruit PcG proteins to the promoters of tumor suppressor genes,resulting in epigenetic gene silencing by influencing chromatin structure and DNA accessibility.Thus,PcG proteins are potential diagnostic markers and targets for new chemoprevention and therapeutic strategies.
文摘The developmental program of seeds is promoted by master regulators that are expressed in a seed-specific manner. Ectopic expression studies reveal that expression of these master regulators and other transcriptional regulators is sufficient to promote seed-associated traits, including generation of somatic embryos. Recent work highlights the importance of chromatin-associated factors in restricting expression of seed-specific genes, in particular PcG proteins and ATP-dependent remodelers. This review summarizes what is known regarding factors that promote zygotic and/or somatic embryogenesis and the chromatin machinery that represses their expression. Characterization of the regulation of seedspecific genes reveals that plant chromatin-based repression systems exhibit broad conservation with and surprising differences from animal repression systems.
文摘Recently, it has been shown that plants contain homologs to the animal Polycomb repressive complex I （PRC1） components BM11 and RINGIA/B. In Arabidopsis, there are three BMIl-like genes, two of which, AtBMIIA and B, are required during post-embryonic plant growth to repress embryonic traits and allow cell differentiation. However, little is known about the third BMIl-like gene, AtBMIIC. In this work, we show that AtBMIIC is only expressed during endosperm and stamen development. AtBMIIC is an imprinted gene expressed from the maternal allele in the endosperm but bialleli- cally expressed in stamen. We found that the characteristic expression pattern of AtBMIIC is the result of a complex epigenetic regulation that involves CG DNA methylation, RNA-directed non-CG DNA methylation （RdDM）, and PcG activity. Our results show the orchestrated interplay of different epigenetic mechanisms in regulating gene expression throughout development, shedding light on the current hypotheses for the origin and mechanism of imprinting in plant endosperm.
文摘Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.
