Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant...Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.展开更多
To the Editor:Eosinophilic fasciitis(EF)is a rare scleroderma-like syndrome of diffuse fascitis and eosino-philia with unknown etiology,and occurs almost equally in both sexes.At onset,the mean age of patients is 40 t...To the Editor:Eosinophilic fasciitis(EF)is a rare scleroderma-like syndrome of diffuse fascitis and eosino-philia with unknown etiology,and occurs almost equally in both sexes.At onset,the mean age of patients is 40 to 50 years.Pinal-Fernandez et al[1] and Jinnin and Yamamoto[2]proposed criteria for EF diagnosis,including sclerotic lesions,cutancous induration,and typical fascial thicken-ing with inflammatory infiltration.展开更多
Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a mo...Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a more generalized disorder of the connective tissue involving a number of organs.SSc is characterized by the thickening of dermal collagen bundles,fibrosis,and vascular abnormalities in the visceral organs.[1]Despite the differences in their morphologic features and clinical presentation,these two diseases do share some characteristics including endothelial cell dysfunction,T helper 2(Th2)cell dominance during immune activation and excess fibrosis of the skin with similar pathologic findings,leading to the hypothesis that SSc and LSc share an underlying mechanism of pathogensis.Currently,multiple lines of evidence suggest that genetic factors may contribute to SSc susceptibility.展开更多
基金This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057)the National Key R&D Program of China(grant number 2019YFA09005400)。
文摘Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.
文摘To the Editor:Eosinophilic fasciitis(EF)is a rare scleroderma-like syndrome of diffuse fascitis and eosino-philia with unknown etiology,and occurs almost equally in both sexes.At onset,the mean age of patients is 40 to 50 years.Pinal-Fernandez et al[1] and Jinnin and Yamamoto[2]proposed criteria for EF diagnosis,including sclerotic lesions,cutancous induration,and typical fascial thicken-ing with inflammatory infiltration.
文摘Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a more generalized disorder of the connective tissue involving a number of organs.SSc is characterized by the thickening of dermal collagen bundles,fibrosis,and vascular abnormalities in the visceral organs.[1]Despite the differences in their morphologic features and clinical presentation,these two diseases do share some characteristics including endothelial cell dysfunction,T helper 2(Th2)cell dominance during immune activation and excess fibrosis of the skin with similar pathologic findings,leading to the hypothesis that SSc and LSc share an underlying mechanism of pathogensis.Currently,multiple lines of evidence suggest that genetic factors may contribute to SSc susceptibility.
