Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that ...Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.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
Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polym...Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polymerized human serum albumin bindingactivity respectively. Both were absent in patients with hepatitis A or HBsAg negative chronic liver di-seases. In biopsy - proven patients with chronic active hepatitis (CAH)B, prevalences of bothmarkers were significantly higher at exacerbation that at remission stage of the disease, and so werein CAH than in chronic asymptomatic HBV carrier (AsC) with normal histology. Besides, the pre-valences were significantly higher in HBeAg positive group than in anti-HBe positive group.However, the polymerized human serum albumin binding activity and the preS2 were undoubtedlynot the same, as the prevalence of the latter was only 56.7% of the former.展开更多
Plant-specific transcriptional regulators called TELOMERE REPEAT BINDING proteins(TRBs)combine two DNA-binding domains,the GH1 domain,which binds to linker DNA and is shared with H1 histones,and the Myb/SANT domain,wh...Plant-specific transcriptional regulators called TELOMERE REPEAT BINDING proteins(TRBs)combine two DNA-binding domains,the GH1 domain,which binds to linker DNA and is shared with H1 histones,and the Myb/SANT domain,which specifically recognizes the telobox DNA-binding site motif.TRB1,TRB2,and TRB3 proteins recruit Polycomb group complex 2(PRC2)to deposit H3K27me3 and JMJ14 to remove H3K4me3 at gene promoters containing telobox motifs to repress transcription.Here,we demonstrate that TRB4 and TRB5,two related paralogs belonging to a separate TRB clade conserved in spermatophytes,regulate the transcription of several hundred genes involved in developmental responses to environmental cues.TRB4 binds to several thousand sites in the genome,mainly at transcription start sites and promoter regions of transcriptionally active and H3K4me3-marked genes,but,unlike TRB1,it is not enriched at H3K27me3-marked gene bodies.However,TRB4 can physically interact with the catalytic components of PRC2,SWINGER,and CURLY LEAF(CLF).Unexpectedly,we show that TRB4 and TRB5 are required for distinctive phenotypic traits observed in clf mutant plants and thus function as transcriptional activators of several hundred CLF-controlled genes,including key flowering genes.We further demonstrate that TRB4 shares multiple target genes with TRB1 and physically and genetically interacts with members of both TRB clades.Collectively,these results reveal that TRB proteins engage in both positive and negative interactions with other members of the family to regulate plant development through both PRC2-dependent and-independent mechanisms.展开更多
Large-intergenic noncoding RNAs （lincRNAs） cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and ge...Large-intergenic noncoding RNAs （lincRNAs） cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a UncRNA （linc1614）, occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 sewed as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes. Moreover, Ezh2, an essential subunit of polycomb repressive complex 2 （PRC2）, physically interacted with linc1614 and contributed to lincRNA-mediated transcriptional silencing. Thus, we propose that the interplay of linc1614 with Sox2 implicates this lincRNA as a recruitment platform that mediates transcriptional silencing by guiding the PRC2 complex to the loci of developmental genes.展开更多
基金financially supported by the National Natural Science Foundation of China,Nos.82172104(to CX),81873767(to HZ)a grant from Jiangsu Provincial Research Hospital,Nos.YJXYY202204(to HZ),YJXYY202204-ZD04(to HZ)+5 种基金a grant from Jiangsu Provincial Key Medical CenterJiangsu Provincial Medical Innovation Center,No.CXZX202212Jiangsu Provincial Medical Key Discipline,No.ZDXK202240the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Technology Project of Nantong,No.MS22022008(to HZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.SJCX21_1457(to WW)。
文摘Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.
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。
文摘Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polymerized human serum albumin bindingactivity respectively. Both were absent in patients with hepatitis A or HBsAg negative chronic liver di-seases. In biopsy - proven patients with chronic active hepatitis (CAH)B, prevalences of bothmarkers were significantly higher at exacerbation that at remission stage of the disease, and so werein CAH than in chronic asymptomatic HBV carrier (AsC) with normal histology. Besides, the pre-valences were significantly higher in HBeAg positive group than in anti-HBe positive group.However, the polymerized human serum albumin binding activity and the preS2 were undoubtedlynot the same, as the prevalence of the latter was only 56.7% of the former.
文摘Plant-specific transcriptional regulators called TELOMERE REPEAT BINDING proteins(TRBs)combine two DNA-binding domains,the GH1 domain,which binds to linker DNA and is shared with H1 histones,and the Myb/SANT domain,which specifically recognizes the telobox DNA-binding site motif.TRB1,TRB2,and TRB3 proteins recruit Polycomb group complex 2(PRC2)to deposit H3K27me3 and JMJ14 to remove H3K4me3 at gene promoters containing telobox motifs to repress transcription.Here,we demonstrate that TRB4 and TRB5,two related paralogs belonging to a separate TRB clade conserved in spermatophytes,regulate the transcription of several hundred genes involved in developmental responses to environmental cues.TRB4 binds to several thousand sites in the genome,mainly at transcription start sites and promoter regions of transcriptionally active and H3K4me3-marked genes,but,unlike TRB1,it is not enriched at H3K27me3-marked gene bodies.However,TRB4 can physically interact with the catalytic components of PRC2,SWINGER,and CURLY LEAF(CLF).Unexpectedly,we show that TRB4 and TRB5 are required for distinctive phenotypic traits observed in clf mutant plants and thus function as transcriptional activators of several hundred CLF-controlled genes,including key flowering genes.We further demonstrate that TRB4 shares multiple target genes with TRB1 and physically and genetically interacts with members of both TRB clades.Collectively,these results reveal that TRB proteins engage in both positive and negative interactions with other members of the family to regulate plant development through both PRC2-dependent and-independent mechanisms.
基金This work was supported by grants from the Ministry of Science and Technology （2016YFA0101300）, the National Natural Science Foundation of China （81530042, 31210103905, 31371510, 31571529, 31571519, 31471250, and 31571390）, the Science and Technology Commission of Shanghai Municipality （15JC1403201）, and the Fundamental Research Funds for the Central Universities （2000219136 and 1500219106）.
文摘Large-intergenic noncoding RNAs （lincRNAs） cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a UncRNA （linc1614）, occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 sewed as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes. Moreover, Ezh2, an essential subunit of polycomb repressive complex 2 （PRC2）, physically interacted with linc1614 and contributed to lincRNA-mediated transcriptional silencing. Thus, we propose that the interplay of linc1614 with Sox2 implicates this lincRNA as a recruitment platform that mediates transcriptional silencing by guiding the PRC2 complex to the loci of developmental genes.
