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Characterization of functional transposable element enhancers in acute myeloid leukemia

Science China(Life Sciences) 2020年第5期63卷 675-687页

作者： Yingying Zeng Yaqiang Cao Rivka Sukenik Halevy Picard Nguyen Denghui Liu Xiaoli Zhang Nadav Ahituv Jing-Dong JHan CAS Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthChinese Academy of Sciences Center for Excellence in Molecular Cell ScienceCollaborative Innovation Center for Genetics and Developmental BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Department of Bioengineering and Therapeutic Sciences University of California San FranciscoSan Francisco 94158USA Institute for Human Genetics University of California San FranciscoSan Francisco 94143USA Sackler School of Medicine Tel-Aviv UniversityTel Aviv 6997801Israel Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative BiologyPeking UniversityBeijing 100871China

transposable elements(TEs)have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes.Acute myeloid leukemia(AML)develops as a consequence of a series of genetic changes in hematopoietic precursor cells,including mutations in epigenetic factors.Here,we set out to study the gene regulatory role of TEs in AML.We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data.We show that a large number of TEs in general,and more specifically mammalian-wide interspersed repeats(MIRs),are more enriched in AML cells than in normal blood cells.We obtained a similar finding when analyzing histone modification data in AML patients.Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis.To functionally validate their regulatory role,we selected 19 MIR regions in AML cells,and tested them for enhancer activity in an AML cell line(Kasumi-1)and a chronic myeloid leukemia(CML)cell line(K562);the results revealed several MIRs to be functional enhancers.Taken together,our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.

关键词： transposable element enhancer promoter MIR acute myeloid leukemia

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Exploring transposable element-based markers to identify allelic variations underlying agronomic traits in rice

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Plant Communications 2022年第3期3卷 59-71页

作者： Haidong Yan David C.Haak Song Li Linkai Huang Aureliano Bombarely School of Plant and Environmental Sciences Virginia TechBlacksburgVA 24061USA Graduate Program in Genetics Bioinformatics and Computational Biology(GBCB)Virginia TechBlacksburgVA 24061USA Department of Grassland Science Animal Science and Technology CollegeSichuan Agricultural UniversityChengdu 611130China Department of Bioscience Universita degli Studi di Milano(UNIMI)20133 MilanoItaly Instituto de Biologıa Molecular y Celular de Plantas(IBMCP) UPV-CSIC46022 ValenciaSpain

transposable elements(TEs)are a major force in the production of new alleles during domestication;nevertheless,their use in association studies has been limited because of their complexity.We have developed a TE genotyping pipeline(TEmarker)and applied it to whole-genome genome-wide association study(GWAS)data from 176 Oryza sativa subsp.japonica accessions to identify genetic elements associated with specific agronomic traits.TE markers recovered a large proportion(69%)of single-nucleotide polymorphism(SNP)-based GWAS peaks,and these TE peaks retained ca.25%of the SNPs.The use of TEs in GWASs may reduce false positives associated with linkage disequilibrium(LD)among SNP markers.A genome scan revealed positive selection on TEs associated with agronomic traits.We found several cases of insertion and deletion variants that potentially resulted from the direct action of TEs,including an allele of LOC_Os11g08410 associated with plant height and panicle length traits.Together,these findings reveal the utility of TE markers for connecting genotype to phenotype and suggest a potential role for TEs in influencing phenotypic variations in rice that impact agronomic traits.

关键词： transposable element marker agronomic trait rice GWAS

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Nitrogen starvation induces genome-wide activation of transposable elements in Arabidopsis

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Journal of Integrative Plant Biology 2022年第12期64卷 2374-2384页

作者： Yue Wang Yi Liu Shaofeng Qu Wenjie Liang Linhua Sun Dong Ci Zhitong Ren Liu-Min Fan Weiqiang Qian State Key Laboratory of Protein and Plant Gene Research School of Advanced Agricultural SciencesPeking UniversityBeijing 100871China School of Life Sciences Peking UniversityBeijing 100871China Peking University Institute of Advanced Agricultural Sciences Weifang 261000China

Nitrogen(N)availability is a major limiting factor for plant growth and agricultural productivity.Although the gene regulation network in response to N starvation has been extensively studied,it remains unknown whether N starvation has an impact on the activity of transposable elements(TEs).Here,we report that TEs can be transcriptionally activated in Arabidopsis under N starvation conditions.Through genetic screening of idm1-14 suppressors,we cloned GLU1,which encodes a glutamate synthase that catalyzes the synthesis of glutamate in the primary N assimilation pathway.We found that glutamate synthase 1(GLU1)and its functional homologs GLU2 and glutamate transport 1(GLT1)are redundantly required for TE silencing,suggesting that N metabolism can regulate TE activity.Transcriptome and methylome analyses revealed that N starvation results in genome-wide TE activation without inducing obvious alteration of DNA methylation.Genetic analysis indicated that N starvationinduced TE activation is also independent of other well-established epigenetic mechanisms,including histone methylation and heterochromatin decondensation.Our results provide new insights into the regulation of TE activity under stressful environments in planta.

关键词： DNA methylation glutamate synthase nitrogen starvation transcriptional gene silencing transposable element

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Functional identification of gene cluster for the aniline metabolic pathway mediated by transposable element

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Science Bulletin 2005年第15期 78-82页

作者： Takeo Masahiro Hyogo 671-2201 Graduate School of Engineering Department of Materials Science and Chemistry Himeji Japan 2167 Shosha University of Hyogo

A convenient and widely applicable method has been developed to clone aniline metabolic gene cluster in this study. Three positive recombinant plasmids pDA1, pDB2 and pDB11 were cloned from genomic library of aniline degradation strain AD9. The result of aniline dioxygenase (AD) activity and catechol 2,3-oxygenase (C23O) activity assay showed that pDA1 and pDB11 contain aniline dioxy-genase genes and catechol 2,3-dioxygenase genes, respectively. The sequence analysis of the total 24.7-kb region revealed that this region contains 25 ORFs, of which 17 genes involve metabolism of aniline. In the gene cluster, the first five genes (tadQTA1A2B) and the subsequent gene (tadR1) were pre-dicted to encode a multi-component aniline dioxygenase and a LysR-type regulator, respectively, while the others (tadD1C1D2C2EFGIJKL) were expected to encode meta- cleavage pathway enzymes for catechol degradation. The gene cluster was surrounded by two IS1071 sequences.

关键词： aniline biodegradation transposable element gene cluster.

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Silencing of transposable elements by piRNAs in Drosophila:An Evolutionary Perspective

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Genomics, Proteomics & Bioinformatics 2017年第3期15卷 164-176页

作者： Shiqi Luo Jian Lu State Key Laboratory of Protein and Plant Gene Research Center for BioinformaticsCollege of Life Sciences and Peking-Tsinghua Center for Life SciencesPeking University Beijing Advanced Innovation Center for Food Nutrition and Human Health College of Food Science and Nutritional EngineeringChina Agricultural University

transposable elements （TEs） are DNA sequences that can move within the genome. TEs have greatly shaped the genomes, transcriptomes, and proteomes of the host organisms through a variety of mechanisms. However, TEs generally disrupt genes and destabilize the host genomes, which substantially reduce fitness of the host organisms. Understanding the genomic distribution and evolutionary dynamics of TEs will greatly deepen our understanding of the TE-mediated bio- logical processes. Most TE insertions are highly polymorphic in Drosophila melanogaster, providing us a good system to investigate the evolution of TEs at the population level. Decades of theoretical and experimental studies have well established ＂transposition-selection＂ population genetics model, which assumes that the equilibrium between TE replication and purifying selection determines the copy number of TEs in the genome. In the last decade, P-element-induced wimpy testis （PIW1）- interacting RNAs （piRNAs） were demonstrated to be master repressors of TE activities in Droso- phila, The discovery of piRNAs revolutionized our understanding of TE repression, because it reveals that the host organisms have evolved an adaptive mechanism to defend against TE invasion. Tremendous progress has been made to understand the molecular mechanisms by which piRNAs repress active TEs, although many details in this process remain to be further explored. The inter- action between piRNAs and TEs well explains the molecular mechanisms underlying hybrid dysge- nesis for the IoR and P-M systems in Drosophila, which have puzzled evolutionary biologists for decades. The piRNA repression pathway provides us an unparalleled system to study the co-evolutionary process between parasites and host organisms.

关键词： transposable element piRNA Hybrid dysgenesis Evolution Drosophila

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Perspectives on studying molecular adaptations of amphibians in the genomic era

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Zoological Research 2020年第4期41卷 351-364页

作者： Yan-Bo Sun Yi Zhang Kai Wang Laboratory of Ecology and Evolutionary Biology Yunnan UniversityKunmingYunnan 650091China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Sam Noble Oklahoma Museum of Natural History and Department of Biology University of OklahomaNormanOklahoma 73072USA

Understanding the genetic mechanisms underlying particular adaptations/phenotypes of organisms is one of the core issues of evolutionary biology.The use of genomic data has greatly advanced our understandings on this issue,as well as other aspects of evolutionary biology,including molecular adaptation,speciation,and even conservation of endangered species.Despite the well-recognized advantages,usages of genomic data are still limited to non-mammal vertebrate groups,partly due to the difficulties in assembling large or highly heterozygous genomes.Although this is particularly the case for amphibians,nonetheless,several comparative and population genomic analyses have shed lights into the speciation and adaptation processes of amphibians in a complex landscape,giving a promising hope for a wider application of genomics in the previously believed challenging groups of organisms.At the same time,these pioneer studies also allow us to realize numerous challenges in studying the molecular adaptations and/or phenotypic evolutionary mechanisms of amphibians.In this review,we first summarize the recent progresses in the study of adaptive evolution of amphibians based on genomic data,and then we give perspectives regarding how to effectively identify key pathways underlying the evolution of complex traits in the genomic era,as well as directions for future research.

关键词： Molecular adaptation Gene subnetwork Phenotypic evolution transposable element Amphibians

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Single-Nucleotide Resolution Mapping of the Gossypium raimondii Transcriptome Reveals a New Mechanism for Alternative Splicing of Introns

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Molecular Plant 2014年第5期7卷 829-840页

作者： Qin Li Guanghui Xiao Yu-Xian Zhu State Key Laboratory of Protein and Plant Gene Research College of Life Sciences Peking University Beijing 100871 China National Center for Plant Gene Research (Beijing) Beijing 100101 China

Alternative splicing （AS） is a vital genetic mechanism that enhances the diversity of eukaryotic transcriptomes. Here, we generated 8.3 Gb high-quality RNA-sequencing data from cotton （Gossypium raimondii） and performed a systematic, comparative analysis of AS events. We mapped 85% of the RNA-sequencing data onto the reference genome and identified 154 368 splice junctions with 16 437 as events in 10197 genes. I ntron retention constituted the majority （40%） of all AS events in G. raimondii. Comparison across 11 eukaryote species showed that intron retention is the most common AS type in higher plants. Although transposable elements （TEs） were found in only 2.9% of all G. raimondii introns, they are present in 43% of the retained introns, suggesting that TE-insertion may be an important mechanism for intron retention during AS. The majority of the TE insertions are concentrated 0-40 nt upstream of the 3＇-splice site, substantially altering the distribution of branch points from preferred positions and reducing the efficiency of intron splicing by decreasing RNA secondary structure flexibility. Our data suggest that TE-insertion-induced changes in branch point-site distribution are important for intron retention-type AS. Our findings may help explain the vast differences in intron-retention frequencies between vertebrates and higher plants.

关键词： cotton RNA-seq alternative splicing transposable element intron retention.

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The agents of natural genome editing

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分子细胞生物学报:英文版 2011年第3期3卷 181-189页

作者： Guenther Witzany Telos–Philosophische Praxis Vogelsangstraße 18cA-5111-BuermoosAustria

The DNA serves as a stable information storage medium and every protein which is needed by the cell is produced from this blueprint via an RNA intermediate code.More recently it was found that an abundance of various RNA elements cooperate in a variety of steps and substeps as regulatory and catalytic units with multiple competencies to act on RNA transcripts.Natural genome editing on one side is the competent agent-driven generation and integration of meaningful DNA nucleotide sequences into pre-existing genomic content arrangements,and the ability to(re-)combine and(re-)regulate them according to context-dependent(i.***.adaptational)purposes of the host organism.Natural genome editing on the other side designates the integration of all RNA activities acting on RNA transcripts without altering DNA-encoded genes.If we take the genetic code seriously as a natural code,there must be agents that are competent to act on this code because no natural code codes itself as no natural language speaks itself.As code editing agents,viral and subviral agents have been suggested because there are several indicators that demonstrate viruses competent in both RNA and DNA natural genome editing.

关键词： persistent virus repetitive element transposable element cooped adaptation riboagent non-coding RNA

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Plant MITEs: Useful Tools for Plant Genetics and Genomics

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Genomics, Proteomics & Bioinformatics 2003年第2期1卷 90-100页

作者： Ying FengAgriculture and Biotechnology College, Zhejiang University, Hangzhou 310029, China Agriculture and Biotechnology College Zhejiang University Hangzhou 310029 China. qzhxue@***

MTTEs (Miniature inverted-repeat transposabie elements) are reminiscence ot non-autonomous DNA (class Ⅱ) elements, which are distinguished from other transposable elements by their small size, short terminal inverted repeats (TIRs), high copy numbers, genie preference, and DNA sequence identity among family members. Although MITEs were first discovered in plants and still actively reshaping genomes, they have been isolated from a wide range of eukaryotic organisms. MITEs can be divided into Tourist-like, Stowaway-like, and pogo-like groups, according to similarities of their TIRs and TSDs (target site duplications). In despite of several models to explain the origin and amplification of MITEs, their mechanisms of transposition and accumulation in eukaryotic genomes remain poorly understood owing to insufficient experimental data. The unique properties of MITEs have been exploited as useful genetic tools for plant genome analysis. Utilization of MITEs as effective and informative genomic markers and potential application of MITEs in plants systematic, phylogenetic, and genetic studies are discussed.

关键词： miniature inverted-repeat transposable element MITE transposable element retrotransposon evolution plant

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An old weapon with a new function:PIWI-interacting RNAs in neurodegenerative diseases

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Translational Neurodegeneration 2021年第1期10卷 91-111页

作者： Xiaobing Huang Garry Wong Centre of Reproduction Development and AgingFaculty of Health SciencesUniversity of MacaoMacao 999078S.A.R.China

PlWI-interacting RNAs(piRNAs)are small non-coding transcripts that are highly conserved across species and regulate gene expression through pre-and post-transcriptional processes.piRNAs were originally discovered in germline cells and protect against transposable element expression to promote and maintain genome stability.In the recent decade,emerging roles of piRNAs have been revealed,including the roles in sterility,tumorigenesis,metabolic homeostasis,neurodevelopment,and neurodegenerative diseases.In this review,we summarize piRNA biogenesis in C.elegans,Drosophila,and mice,and further elaborate upon how piRNAs mitigate the harmful effects of transposons.Lastly,the most recent findings on piRNA participation in neurological diseases are highlighted.We speculate on the mechanisms of piRNA action in the development and progression of neurodegenerative diseases.Understanding the roles of piRNAs in neurological diseases may facilitate their applications in diagnostic and therapeutic practice.

关键词： piRNA piRNA biogenesis transposable element Neurodegenerative disease H3K9me3

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