In recent years,environmental DNA(e DNA)has garnered significant attention as a novel tool in biodiversity monitoring,recognized for its efficiency,convenience,and non-invasiveness.Despite its extensive application in...In recent years,environmental DNA(e DNA)has garnered significant attention as a novel tool in biodiversity monitoring,recognized for its efficiency,convenience,and non-invasiveness.Despite its extensive application in various ecological studies,such as conservation,invasion biology,biomonitoring and biodiversity survey assessment,its use in avian monitoring remains in its infancy.This review critically examines the potential and limitations of e DNA technology for avian monitoring,focusing on current advancements and ongoing challenges in this emerging field.Water and air are the primary environmental media for collecting avian e DNA,although other sources like spider webs and plant flowers have been explored as well.Notably,airborne e DNA has been reported to capture the highest diversity of avian species.While avian e DNA technology has shown promise for monitoring rare and endangered species and assessing avian diversity,significant challenges remain,particularly in sampling strategies,DNA extraction methodology,primer selection,and ascertain abundance.Additionally,we discussed the factors influencing the production,transportation,and degradation of avian e DNA in the environment.Finally,we suggested future research directions,including optimizing sampling strategies,developing avian-specific universal primers,expanding avian DNA barcode databases,enhancing e DNA detectability,and integrating environmental RNA(e RNA)and e DNA approaches.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
Enhancers modulate gene expression by interacting with promoters.Models of enhancer-promoter interactions(EPIs)in the literature involve the activity of many components,including transcription factors and nucleic acid...Enhancers modulate gene expression by interacting with promoters.Models of enhancer-promoter interactions(EPIs)in the literature involve the activity of many components,including transcription factors and nucleic acid.However,the role that sequence similarity plays in EPIs remains largely unexplored.Herein,we report that Alu-derived sequences dominate sequence similarity between enhancers and promoters.After rejecting alternative DNA:DNA and DNA:RNA triplex models,we propose that enhancer-associated RNAs(eRNAs)may directly contact their targeted promoters by forming trans-acting R-loops at those Alu sequences.We show how the characteristic distribution of functional genomic data,such as RNA-DNA proximate ligation reads,binding of transcription factors,and RNA-binding proteins,all align with the Alu sequences of EPIs.We also show that these aligned Alu sequences may be subject to the constraint of coevolution,further implying the functional significance of these R-loop hybrids.Finally,our results imply that eRNA and Alu elements associate in a manner previously unrecognized in EPIs and the evolution of gene regulation networks in mammals.展开更多
Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory...Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.展开更多
Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.I...Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.In this study,we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues.By incorporating chromatin immunoprecipitation sequencing data,we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.Among these,lactotransferrin-eRNA(LTFe)was markedly downregulated in prostate cancer tissues,with functional analyses revealing its tumor-suppressive role.Mechanistically,LTFe promotes the transcription of its target gene,lactotransferrin(LTF),by interacting with heterogeneous nuclear ribonucleoprotein F(HNRNPF)and facilitating enhancer-promoter chromatin interactions.Furthermore,we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport.Notably,androgen receptor(AR)signaling disrupts LTFe-associated chromatin looping,leading to ferroptosis resistance.Therapeutically,co-administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth,offering a promising strategy for castrationresistant prostate cancer.Collectively,this study provides novel insights into the mechanistic role of eRNAs in prostate cancer,highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.展开更多
The use of environmental DNA(eDNA)has significantly revolutionized studies in biodiversity science.A crucial innovation of eDNA-based biodiversity assessment is the ability to detect species through genetic materials ...The use of environmental DNA(eDNA)has significantly revolutionized studies in biodiversity science.A crucial innovation of eDNA-based biodiversity assessment is the ability to detect species through genetic materials released by organisms into their environments,without the need for direct observation or capture(i.e.,organisms remain“unseen”).The fact that organisms remain“unseen”has many pros and cons,many of which have been largely recognized and technically addressed or managed.However,two recent studies have both highlighted another critical issue regarding eDNA-based biodiversity assessments:the prevalence of overlooked eDNA contamination originating from human activities,such as the release of treated wastewater into aquatic ecosystems.Such eDNA contamination derived from human activities can lead to significant false positive errors in eDNA-based biodiversity assessments,particularly in human-disturbed ecosystems such as urban and coastal environments.Here I discuss the causes and consequences of eDNA contamination,stressing that this widespread but often neglected issue can substantially affect both eDNA-based theoretical studies and applied biodiversity management.Additionally,I propose several potential technical solutions to minimize its negative impacts,including well-designed sampling strategies,a deeper understanding of eDNA persistence and its spread in local waterbodies,and the use of environmental RNA(eRNA).Given that eDNA contamination can significantly impact ecosystems such as urban and coastal environments where biodiversity provides essential ecosystem services,I call for precautionary approaches and technical efforts to mitigate false positives derived from eDNA contamination in biodiversity assessments in these ecosystems.展开更多
Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription.Meanwhile,active enhancers and super-enhancers also produce transcripts terme...Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription.Meanwhile,active enhancers and super-enhancers also produce transcripts termed enhancer RNAs(eRNAs) from their DNA elements.Although enhancers have been identified for more than 30 years,widespread transcription from enhancers are just discovered by genome-wide sequencing and considered as the key to understand longstanding questions in gene transcription.RNA-transcribed enhancers are marked by histone modifications such as H3K4m1/2 and H3K27Ac,and enriched with transcription regulatory factors such as LDTFs,P300,CBP,BRD4 and MED1.Those regulatory factors might constitute a Mega-Trans-like complex to potently activate enhancers.Compared to mRNAs,eRNAs are quite unstable and play roles at local.Functionally,it has been shown that e RNAs promote formation of enhancer-promoter loops.Several studies also demonstrated that eRNAs help the binding of RNA polymerase II(RNAPII) or transition of paused RNAPII by de-association of the negative elongation factor(NELF) complex.Nevertheless,these proposed mechanisms are not universally accepted and still under controversy.Here,we comprehensively summarize the reported findings and make perspectives for future exploration.We also believe that super-enhancer derived RNAs(seRNAs) might be informative to understand the nature of super-enhancers.展开更多
Enhancer-derived RNAs （eRNAs） are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA prod...Enhancer-derived RNAs （eRNAs） are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA production and enhancer activity has stimulated studies on the potential role of eRNAs in transcriptional regulation. Additionally, eRNA has also served as a marker for global identification of enhancers. Here I review the brief history and fascinating properties of eRNAs.展开更多
基金supported by the Key Research and Development Project of Tianjin,China(23YFZCSN00040)。
文摘In recent years,environmental DNA(e DNA)has garnered significant attention as a novel tool in biodiversity monitoring,recognized for its efficiency,convenience,and non-invasiveness.Despite its extensive application in various ecological studies,such as conservation,invasion biology,biomonitoring and biodiversity survey assessment,its use in avian monitoring remains in its infancy.This review critically examines the potential and limitations of e DNA technology for avian monitoring,focusing on current advancements and ongoing challenges in this emerging field.Water and air are the primary environmental media for collecting avian e DNA,although other sources like spider webs and plant flowers have been explored as well.Notably,airborne e DNA has been reported to capture the highest diversity of avian species.While avian e DNA technology has shown promise for monitoring rare and endangered species and assessing avian diversity,significant challenges remain,particularly in sampling strategies,DNA extraction methodology,primer selection,and ascertain abundance.Additionally,we discussed the factors influencing the production,transportation,and degradation of avian e DNA in the environment.Finally,we suggested future research directions,including optimizing sampling strategies,developing avian-specific universal primers,expanding avian DNA barcode databases,enhancing e DNA detectability,and integrating environmental RNA(e RNA)and e DNA approaches.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
基金the National Natural Science Foundation of China of China(91940304,31871331,31671342)Beijing Natural Science Foundation(Z200021)+2 种基金Special Investigation on Science and Technology Basic Resources of MOST,China(2019FY100102)the National Key R&D Program of China(2018YFC2000400)the Beijing Advanced Discipline Fund(115200S001)。
文摘Enhancers modulate gene expression by interacting with promoters.Models of enhancer-promoter interactions(EPIs)in the literature involve the activity of many components,including transcription factors and nucleic acid.However,the role that sequence similarity plays in EPIs remains largely unexplored.Herein,we report that Alu-derived sequences dominate sequence similarity between enhancers and promoters.After rejecting alternative DNA:DNA and DNA:RNA triplex models,we propose that enhancer-associated RNAs(eRNAs)may directly contact their targeted promoters by forming trans-acting R-loops at those Alu sequences.We show how the characteristic distribution of functional genomic data,such as RNA-DNA proximate ligation reads,binding of transcription factors,and RNA-binding proteins,all align with the Alu sequences of EPIs.We also show that these aligned Alu sequences may be subject to the constraint of coevolution,further implying the functional significance of these R-loop hybrids.Finally,our results imply that eRNA and Alu elements associate in a manner previously unrecognized in EPIs and the evolution of gene regulation networks in mammals.
基金This work was supported by the Key R&D Programmes of Guangdong Province,China(2018B020203003)the National Natural Science Foundation of China(31830090)+1 种基金the Shenzhen Science Technology and Innovation Commission,China(JCYJ20170307160516413)and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ZDRW202006).We appreciate Postdoctoral Fellow AdeyinkaAbiolaAdetula,for grammar checking and suggestions.
文摘Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.
基金supported by the National Natural Science Foundation of China(Nos.82373333,82173068)to Z.Wang,and Nos.82073082,82311530050 to G.-H.Wei+2 种基金the Hubei Natural Science Foundation Innovation Development Joint Fund Key Project(2024AFD420 to Z.Wang)the National Key Research and Development Program of China(2022YFC2703600 to G.-H.Wei)Z.X.Wang was supported by the National Natural Science Foundation of China(82203416)。
文摘Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.In this study,we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues.By incorporating chromatin immunoprecipitation sequencing data,we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.Among these,lactotransferrin-eRNA(LTFe)was markedly downregulated in prostate cancer tissues,with functional analyses revealing its tumor-suppressive role.Mechanistically,LTFe promotes the transcription of its target gene,lactotransferrin(LTF),by interacting with heterogeneous nuclear ribonucleoprotein F(HNRNPF)and facilitating enhancer-promoter chromatin interactions.Furthermore,we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport.Notably,androgen receptor(AR)signaling disrupts LTFe-associated chromatin looping,leading to ferroptosis resistance.Therapeutically,co-administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth,offering a promising strategy for castrationresistant prostate cancer.Collectively,this study provides novel insights into the mechanistic role of eRNAs in prostate cancer,highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.
基金funded by the National Key Research and Development Program of China(grant number:2021YFC3200102)Guiding Funds of Central Government for Supporting the Development of Local Science and Technology(grant number:2024ZY0128)Yunnan Collaborative Innovation Center for Plateau Lake Ecology and Environmental Health.
文摘The use of environmental DNA(eDNA)has significantly revolutionized studies in biodiversity science.A crucial innovation of eDNA-based biodiversity assessment is the ability to detect species through genetic materials released by organisms into their environments,without the need for direct observation or capture(i.e.,organisms remain“unseen”).The fact that organisms remain“unseen”has many pros and cons,many of which have been largely recognized and technically addressed or managed.However,two recent studies have both highlighted another critical issue regarding eDNA-based biodiversity assessments:the prevalence of overlooked eDNA contamination originating from human activities,such as the release of treated wastewater into aquatic ecosystems.Such eDNA contamination derived from human activities can lead to significant false positive errors in eDNA-based biodiversity assessments,particularly in human-disturbed ecosystems such as urban and coastal environments.Here I discuss the causes and consequences of eDNA contamination,stressing that this widespread but often neglected issue can substantially affect both eDNA-based theoretical studies and applied biodiversity management.Additionally,I propose several potential technical solutions to minimize its negative impacts,including well-designed sampling strategies,a deeper understanding of eDNA persistence and its spread in local waterbodies,and the use of environmental RNA(eRNA).Given that eDNA contamination can significantly impact ecosystems such as urban and coastal environments where biodiversity provides essential ecosystem services,I call for precautionary approaches and technical efforts to mitigate false positives derived from eDNA contamination in biodiversity assessments in these ecosystems.
基金supported by the Distinguished Professorship Program of Jiangsu Province to Y.Fthe National Natural Science Foundation of China(31770935,81641164,81600386,81471539,30801350)+2 种基金the Natural Science Foundation of Nantong University(14Z022)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX17_1933)Undergraduate Training Program for Innovation(201710304030Z)
文摘Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription.Meanwhile,active enhancers and super-enhancers also produce transcripts termed enhancer RNAs(eRNAs) from their DNA elements.Although enhancers have been identified for more than 30 years,widespread transcription from enhancers are just discovered by genome-wide sequencing and considered as the key to understand longstanding questions in gene transcription.RNA-transcribed enhancers are marked by histone modifications such as H3K4m1/2 and H3K27Ac,and enriched with transcription regulatory factors such as LDTFs,P300,CBP,BRD4 and MED1.Those regulatory factors might constitute a Mega-Trans-like complex to potently activate enhancers.Compared to mRNAs,eRNAs are quite unstable and play roles at local.Functionally,it has been shown that e RNAs promote formation of enhancer-promoter loops.Several studies also demonstrated that eRNAs help the binding of RNA polymerase II(RNAPII) or transition of paused RNAPII by de-association of the negative elongation factor(NELF) complex.Nevertheless,these proposed mechanisms are not universally accepted and still under controversy.Here,we comprehensively summarize the reported findings and make perspectives for future exploration.We also believe that super-enhancer derived RNAs(seRNAs) might be informative to understand the nature of super-enhancers.
基金the support of Shanghai Pu Jiang Programstartup fund from the National Research Center for Translational Medicine(Shanghai),the State Key Laboratory for Medical Genomics,Shanghai Institute of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,China
文摘Enhancer-derived RNAs （eRNAs） are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA production and enhancer activity has stimulated studies on the potential role of eRNAs in transcriptional regulation. Additionally, eRNA has also served as a marker for global identification of enhancers. Here I review the brief history and fascinating properties of eRNAs.
