It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional patter...It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional pattern is less characterized except for the role ofcis-regulatory evolution. Epigenetic modification offers an alternative possibility. Here, we examined how histone modifications have changed among different gene age groups in Drosophila melanogaster by integrative analyses of an updated new gene dataset and published epigenomic data. We found a robust pattern across various datasets where both the coverage and intensity of active histone modifications, histone 3 lysine 4 trimethylation and lysine 36 trimethylation, increased with evolutionary age. Such a temporal correlation is negative and much weaker for the repressive histone mark, lysine 9 trimethylation, which is expected given its major association with heterochromatin. By further comparison with neighboring old genes, the depletion of active marks of new genes could be only partially explained by the local epigenetic context. All these data are consistent with the observation that older genes bear relatively higher expression levels and suggest that the evolution of histone modifications could be implicated in transcriptional evolution after gene birth.展开更多
Genomic imprinting is often associated with aUele-specific epigenetic modifications. Although many reports suggested potential roles of DNA methylation and H3K27me3 in regulating genomic imprinting, the contribu- tion...Genomic imprinting is often associated with aUele-specific epigenetic modifications. Although many reports suggested potential roles of DNA methylation and H3K27me3 in regulating genomic imprinting, the contribu- tions of allele-specific active histone modifications to imprinting remain still unclear in plants. Here, we report the identification of 337 high-stringency allele-specific H3K4me3 and H3K36me3 peaks in maize endosperm. Paternally preferred H3K4me3 and H3K36me3 peaks mostly co-localized with paternally expressed genes （PEGs）, while endosperm-specific maternally expressed genes （endo-MEGs） were associated with mater- nally preferred H3K4me3 and H3K36me3 peaks. A unique signature for PEGs was observed, where the active H3K4me4 and H3K36me3 as well as repressive H3K27me3 appeared together. At the gene body of con-PEGs （constitutively expressed PEG）, H3K27me3 and H3K36me3 were specifically deposited on hypomethylated maternal alleles and hypermethylated paternal alleles, respectively. Around the transcription start sites of endo-MEGs, DNA methylation and H3K4me3 specifically marked paternal and maternal alleles, respectively. In addition, 35 maternally expressed non-coding RNAs exhibited the same allele-specific epigenetic features as endo-MEGs, indicating similar mechanisms for the regulation of imprinted genes and non-coding RNAs. Taken together, our results uncover the complex patterns of mutually exclusive epigenetic modifications deposited at different alleles of imprinted genes that are required for genomic imprinting in maize endosperm.展开更多
Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylati...Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA PolⅡ(RNA PolⅡSer2P),and Ser5-phosphorylated RNA PolⅡ(RNA PolⅡSer5 P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA PolⅡSer2P and Ser5P.展开更多
Di-and tri-methylation of lysine 36 on histone H3(H3K36me2/3)is catalysed by histone methyltransferase Set2,which plays an essential role in transcriptional regulation.Although there is a single H3K36 methyltransferas...Di-and tri-methylation of lysine 36 on histone H3(H3K36me2/3)is catalysed by histone methyltransferase Set2,which plays an essential role in transcriptional regulation.Although there is a single H3K36 methyltransferase in yeast and higher eukaryotes,two H3K36 methyltransferases,Ash1 and Set2,were present in many filamentous fungi.However,their roles in H3K36 methylation and transcriptional regulation remained unclear.Combined with methods of RNA-seq and ChIP-seq,we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae,which causes the devastating worldwide rice blast disease.Ash1 and Set2 distinguish genomic H3K36me2/3-marked regions and are differentially associated with repressed and activated transcription,respectively.Furthermore,Ash1-catalysed H3K36me2 was co-localized with H3K27me3 at the chromatin,and Ash1 was required for the enrichment and transcriptional silencing of H3K27me3-occupied genes.With the different roles of Ash1 and Set2,in H3K36me2/3 enrichment and transcriptional regulation on the stress-responsive genes,they differentially respond to various stresses in M.oryzae.Overall,we reveal a novel mechanism by which two H3K36 methyltransferases catalyze H3K36me2/3 that differentially associate with transcriptional activities and contribute to enrichment of facultative heterochromatin in eukaryotes.展开更多
文摘It is known that evolutionarily new genes can rapidly evolve essential roles in fundamental biological processes. Nevertheless, the underlying molecular mechanism of how they acquire theft novel transcriptional pattern is less characterized except for the role ofcis-regulatory evolution. Epigenetic modification offers an alternative possibility. Here, we examined how histone modifications have changed among different gene age groups in Drosophila melanogaster by integrative analyses of an updated new gene dataset and published epigenomic data. We found a robust pattern across various datasets where both the coverage and intensity of active histone modifications, histone 3 lysine 4 trimethylation and lysine 36 trimethylation, increased with evolutionary age. Such a temporal correlation is negative and much weaker for the repressive histone mark, lysine 9 trimethylation, which is expected given its major association with heterochromatin. By further comparison with neighboring old genes, the depletion of active marks of new genes could be only partially explained by the local epigenetic context. All these data are consistent with the observation that older genes bear relatively higher expression levels and suggest that the evolution of histone modifications could be implicated in transcriptional evolution after gene birth.
文摘Genomic imprinting is often associated with aUele-specific epigenetic modifications. Although many reports suggested potential roles of DNA methylation and H3K27me3 in regulating genomic imprinting, the contribu- tions of allele-specific active histone modifications to imprinting remain still unclear in plants. Here, we report the identification of 337 high-stringency allele-specific H3K4me3 and H3K36me3 peaks in maize endosperm. Paternally preferred H3K4me3 and H3K36me3 peaks mostly co-localized with paternally expressed genes （PEGs）, while endosperm-specific maternally expressed genes （endo-MEGs） were associated with mater- nally preferred H3K4me3 and H3K36me3 peaks. A unique signature for PEGs was observed, where the active H3K4me4 and H3K36me3 as well as repressive H3K27me3 appeared together. At the gene body of con-PEGs （constitutively expressed PEG）, H3K27me3 and H3K36me3 were specifically deposited on hypomethylated maternal alleles and hypermethylated paternal alleles, respectively. Around the transcription start sites of endo-MEGs, DNA methylation and H3K4me3 specifically marked paternal and maternal alleles, respectively. In addition, 35 maternally expressed non-coding RNAs exhibited the same allele-specific epigenetic features as endo-MEGs, indicating similar mechanisms for the regulation of imprinted genes and non-coding RNAs. Taken together, our results uncover the complex patterns of mutually exclusive epigenetic modifications deposited at different alleles of imprinted genes that are required for genomic imprinting in maize endosperm.
基金supported by Singapore National Medical Research Council(Grant No.CBRG14nov065)the Macao Science and Technology Development Fund,China(Grant No.FDCT-18-033-SKL-016A)。
文摘Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA PolⅡ(RNA PolⅡSer2P),and Ser5-phosphorylated RNA PolⅡ(RNA PolⅡSer5 P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA PolⅡSer2P and Ser5P.
基金supported by the National Natural Science Foundation of China (32170192 and 32370200 to Z.T)National Youth Talent Support Program.
文摘Di-and tri-methylation of lysine 36 on histone H3(H3K36me2/3)is catalysed by histone methyltransferase Set2,which plays an essential role in transcriptional regulation.Although there is a single H3K36 methyltransferase in yeast and higher eukaryotes,two H3K36 methyltransferases,Ash1 and Set2,were present in many filamentous fungi.However,their roles in H3K36 methylation and transcriptional regulation remained unclear.Combined with methods of RNA-seq and ChIP-seq,we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae,which causes the devastating worldwide rice blast disease.Ash1 and Set2 distinguish genomic H3K36me2/3-marked regions and are differentially associated with repressed and activated transcription,respectively.Furthermore,Ash1-catalysed H3K36me2 was co-localized with H3K27me3 at the chromatin,and Ash1 was required for the enrichment and transcriptional silencing of H3K27me3-occupied genes.With the different roles of Ash1 and Set2,in H3K36me2/3 enrichment and transcriptional regulation on the stress-responsive genes,they differentially respond to various stresses in M.oryzae.Overall,we reveal a novel mechanism by which two H3K36 methyltransferases catalyze H3K36me2/3 that differentially associate with transcriptional activities and contribute to enrichment of facultative heterochromatin in eukaryotes.
