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
Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universall...Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.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
B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known a...B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known as a critical regulator in cellular physiology, BMI1 is essential in self-renewal and differentiation in different lineages of stem cells. BMI1 also plays a significant role in cancer etiology for its involvement in pathological progress such as epithelial–mesenchymal transition (EMT) and cancer stem cell maintenance, propagation, and differentiation. Importantly, overexpression of BMI1 is predictive for drug resistance, tumor recurrence, and eventual therapy failure of various cancer subtypes, which renders the pharmacological targeting at BMI1 as a novel and promising therapeutic approach. The study on prostate cancer, a prevalent hormone-related cancer among men, has promoted enormous research advancements in cancer genetics and epigenetics. This review summarizes the role of BMI1 as an oncogenic and epigenetic regulator in tumor initiation, progression, and relapse of prostate cancer.展开更多
From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which Pe...From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which PeG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identi- fied in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex （PRC）I components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components.展开更多
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This work was supported by Natural Science Foundation of China(Nos.81903770,81973177,and 22277110,China)Joint Funds of Technology Research and Development Plan of Henan Province(No.232301420058,China)+5 种基金China Postdoctoral Science Foundation(No.2019M662556,China)Key scientific and technological projects of Henan Province(No.222102310125,China)Natural Science Foundation of Henan Province(No.222300420069,China)Program for Science&Technology Innovation Talents in Universities of Henan Province(No.21HASTIT045,China)Cultivation Project of Zhengzhou University(JC23852097,China)Tianjian Laboratory of Advanced Biomedical Sciences,and the open fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,China(No.KF-202303,China).
文摘Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.
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.
文摘B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known as a critical regulator in cellular physiology, BMI1 is essential in self-renewal and differentiation in different lineages of stem cells. BMI1 also plays a significant role in cancer etiology for its involvement in pathological progress such as epithelial–mesenchymal transition (EMT) and cancer stem cell maintenance, propagation, and differentiation. Importantly, overexpression of BMI1 is predictive for drug resistance, tumor recurrence, and eventual therapy failure of various cancer subtypes, which renders the pharmacological targeting at BMI1 as a novel and promising therapeutic approach. The study on prostate cancer, a prevalent hormone-related cancer among men, has promoted enormous research advancements in cancer genetics and epigenetics. This review summarizes the role of BMI1 as an oncogenic and epigenetic regulator in tumor initiation, progression, and relapse of prostate cancer.
文摘From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which PeG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identi- fied in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex （PRC）I components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components.
