Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,in...Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.展开更多
Programmed DNA double-strand break(DSB)formation is a crucial step in meiotic recombination,yet techniques for highefficiency and precise mapping of the 3’ends of DSBs are still in their infancy.Here,we report a nove...Programmed DNA double-strand break(DSB)formation is a crucial step in meiotic recombination,yet techniques for highefficiency and precise mapping of the 3’ends of DSBs are still in their infancy.Here,we report a novel technique,named DNA End tailing and sequencing(DEtail-seq),which can directly and ultra-efficiently characterize the 3’ends of meiotic DSBs with near single-nucleotide resolution in a variety of species,including yeast,mouse,and human.We find that the 3’ends of meiotic DSBs are stable without significant resection in budding yeast.Meiotic DSBs are strongly enriched in de novo H3K4me3 peaks in the mouse genome at leptotene stage.We also profile meiotic DSBs in human and find DSB hotspots are enriched near the common fragile sites during human meiosis,especially at CCCTC-binding factor(CTCF)-associated enhancers.Therefore,DEtail-seq provides a powerful method to detect DSB ends in various species,and our results provide new insights into the distribution and regulation of meiotic DSB hotspots.展开更多
R-loops are chromatin structures consisting of anRNA:DNA hybrid and the other single-stranded DNA,which widely exist among genomes from bacteria to higher eukaryotes and participate in a variety of biological processe...R-loops are chromatin structures consisting of anRNA:DNA hybrid and the other single-stranded DNA,which widely exist among genomes from bacteria to higher eukaryotes and participate in a variety of biological processes(Zhou et al.,2022).Currently,a variety of approaches to detect genome-wide R-loops have been developed,and ssDRIP-seq(single-strand DNA ligation-based library preparation from DNA:RNA hybrid immunoprecipitation,followed by sequencing)is one of the widely utilized methods(Xu et al.,2022).However,there are many limitations to genome-wide R-loop mapping based on high-throughput methods.For example,the activity of restriction enzymes for genomic DNA fragmentation.展开更多
R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essen...R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root archi- tecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new in- sights into transcriptional regulation of hormone signaling in plants.展开更多
Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHO...Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHORT DAYS(EFS)is the major contributor for H3K36 methylation in Arabidopsis and is important for plant development.Here,we find that EFS is expressed in different stages of embryo morphogenesis,and the efs mutant produces larger embryo that results in enlarged seeds.Further analysis reveals that an imprinted gene MOP9.5 is hypomethylated at the promoter region and its expression is derepressed in efs mutant.MOP9.5 promoter is marked by various epigenetic modifications,and we find that following the increase of H3K36me3,H3K27me3 and H3K9me2 levels are reduced in efs mutant.This data indicates an antagonistic regulation between H3K36me3 and DNA methylation,and/or H3K27me3 at MOP9.5.Our results further show that both maternal and paternal EFS alleles are responsible for the seed size regulation,which unraveled a novel function of EFS in plant development.展开更多
An R-loop is a three-stranded chromatin structure that consists of a displaced single strand of DNA and an RNA:DNA hybrid duplex,which was thought to be a rare by-product of transcription.However,recent genome-wide da...An R-loop is a three-stranded chromatin structure that consists of a displaced single strand of DNA and an RNA:DNA hybrid duplex,which was thought to be a rare by-product of transcription.However,recent genome-wide data have shown that R-loops are widespread and pervasive in a variety of genomes,and a growing body of experimental evidence indicates that R-loops have both beneficial and harmful effects on an organism.To maximize benefit and avoid harm,organisms have evolved several means by which they tightly regulate R-loop levels.Here,we summarize our current understanding of the biogenesis and effects of R-loops,the mechanisms that regulate them,and methods of R-loop profiling,reviewing recent research advances on R-loops in plants.Furthermore,we provide perspectives on future research directions for R-loop biology in plants,which might lead to a more comprehensive understanding of R-loop functions in plant genome regulation and contribute to future agricultural improvements.展开更多
Three-stranded chromatin structure R-loops are thought to be formed co-transcriptionally with newly synthesized RNA behind RNA polymerases,and play essential biological roles(Costantino and Koshland,2015;Santos-Pereir...Three-stranded chromatin structure R-loops are thought to be formed co-transcriptionally with newly synthesized RNA behind RNA polymerases,and play essential biological roles(Costantino and Koshland,2015;Santos-Pereira and Aguilera,2015;Crossley et al.,2019;Garcia-Muse and Aguilera,2019;Niehrs and Luke,2020;Zhou et al .,2022).展开更多
基金supported by the grants from the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.:2021-I2M-1-026)the Beijing Natural Science Foundation of China(Grant Nos.:7212155 and 7162135).
文摘Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.
基金supported by the National Natural Science Foundation of China (91740105,31822028,32071437,31900302)Central Public-interest Scientific Institution Basal Research Fund (Y2022QC33)。
文摘Programmed DNA double-strand break(DSB)formation is a crucial step in meiotic recombination,yet techniques for highefficiency and precise mapping of the 3’ends of DSBs are still in their infancy.Here,we report a novel technique,named DNA End tailing and sequencing(DEtail-seq),which can directly and ultra-efficiently characterize the 3’ends of meiotic DSBs with near single-nucleotide resolution in a variety of species,including yeast,mouse,and human.We find that the 3’ends of meiotic DSBs are stable without significant resection in budding yeast.Meiotic DSBs are strongly enriched in de novo H3K4me3 peaks in the mouse genome at leptotene stage.We also profile meiotic DSBs in human and find DSB hotspots are enriched near the common fragile sites during human meiosis,especially at CCCTC-binding factor(CTCF)-associated enhancers.Therefore,DEtail-seq provides a powerful method to detect DSB ends in various species,and our results provide new insights into the distribution and regulation of meiotic DSB hotspots.
基金supported by the Digitalization,Development,and Application of Biotic Resource Project(202002AA100007 to C.Z.)the National Natural Science Foundation of China(grant nos.31822028 and 91940306 to Q.S.and 32100428 to J.Z.)and the Ministry of Science and Technology of the People’s Republic of China(2016YFA0500800 to Q.S.).We greatly appreciate the useful discussions by all the members from the Zhang lab and the Sun lab.The Zhang Lab is supported by the Yunnan Young&Elite Talents Project(YNWR-QNBJ-2019-268).J.Z.is supported by the postdoctoral fellowship from Tsinghua-Peking Center for Life Sciences.
文摘R-loops are chromatin structures consisting of anRNA:DNA hybrid and the other single-stranded DNA,which widely exist among genomes from bacteria to higher eukaryotes and participate in a variety of biological processes(Zhou et al.,2022).Currently,a variety of approaches to detect genome-wide R-loops have been developed,and ssDRIP-seq(single-strand DNA ligation-based library preparation from DNA:RNA hybrid immunoprecipitation,followed by sequencing)is one of the widely utilized methods(Xu et al.,2022).However,there are many limitations to genome-wide R-loop mapping based on high-throughput methods.For example,the activity of restriction enzymes for genomic DNA fragmentation.
基金This work was supported by the National Natural Science Foundation of China （30900070, to C.C.）, Tsinghua University initiative Scientific Research Program, Tsinghua-Peking Joint Center for Life Sciences, and 1000 Young Talent Program of China （to The Sun Lab）. S.S. and E.W. were supported by postdoctoral fellowships from Tsinghua-Peking Joint Center for Life Sciences.
文摘R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root archi- tecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new in- sights into transcriptional regulation of hormone signaling in plants.
基金supported by National Key R&D Program (2016YFA0500800)the National Natural Science Foundation of China (31571322)+2 种基金Tsinghua-Peking Joint Center for Life Sciences1000 Young Talent Program of ChinaS.Shafiq and Wei Xu are supported by the postdoctoral fellowships from Tsinghua-Peking Joint Center for Life Sciences
文摘Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHORT DAYS(EFS)is the major contributor for H3K36 methylation in Arabidopsis and is important for plant development.Here,we find that EFS is expressed in different stages of embryo morphogenesis,and the efs mutant produces larger embryo that results in enlarged seeds.Further analysis reveals that an imprinted gene MOP9.5 is hypomethylated at the promoter region and its expression is derepressed in efs mutant.MOP9.5 promoter is marked by various epigenetic modifications,and we find that following the increase of H3K36me3,H3K27me3 and H3K9me2 levels are reduced in efs mutant.This data indicates an antagonistic regulation between H3K36me3 and DNA methylation,and/or H3K27me3 at MOP9.5.Our results further show that both maternal and paternal EFS alleles are responsible for the seed size regulation,which unraveled a novel function of EFS in plant development.
基金the National Natural Science Foundation of China(Grant Nos.91740105 and 31822028 to Q.Sun32100428 to J.Zhou+2 种基金and 32070651 to W.Zhang)supported by the Tsinghua-Peking Center for Life Sciencessupported by postdoc fellowships from the Tsinghua-Peking Center for Life Sciences。
文摘An R-loop is a three-stranded chromatin structure that consists of a displaced single strand of DNA and an RNA:DNA hybrid duplex,which was thought to be a rare by-product of transcription.However,recent genome-wide data have shown that R-loops are widespread and pervasive in a variety of genomes,and a growing body of experimental evidence indicates that R-loops have both beneficial and harmful effects on an organism.To maximize benefit and avoid harm,organisms have evolved several means by which they tightly regulate R-loop levels.Here,we summarize our current understanding of the biogenesis and effects of R-loops,the mechanisms that regulate them,and methods of R-loop profiling,reviewing recent research advances on R-loops in plants.Furthermore,we provide perspectives on future research directions for R-loop biology in plants,which might lead to a more comprehensive understanding of R-loop functions in plant genome regulation and contribute to future agricultural improvements.
基金the Beijing Advanced Innovation Center for Structural Biology for facility and financial supportsupported by grants from Beijing Advanced Innovation Center for Structural Biology (Number 041301470)
文摘Three-stranded chromatin structure R-loops are thought to be formed co-transcriptionally with newly synthesized RNA behind RNA polymerases,and play essential biological roles(Costantino and Koshland,2015;Santos-Pereira and Aguilera,2015;Crossley et al.,2019;Garcia-Muse and Aguilera,2019;Niehrs and Luke,2020;Zhou et al .,2022).
