Dynamic silencing of somatic L1 retrotransposon insertions reflects the developmental and cellular contexts of their genomic integration.

Abstract:

BACKGROUND:The ongoing mobilization of mammalian transposable elements (TEs) contributes to natural genetic variation. To survey the epigenetic control and expression of reporter genes inserted by L1 retrotransposition in diverse cellular and genomic contexts, we engineered highly sensitive, real-time L1 retrotransposon reporter constructs. RESULTS:Here we describe different patterns of expression and epigenetic controls of newly inserted sequences retrotransposed by L1 in various somatic cells and tissues including cultured human cancer cells, mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and their progeny. In cancer cell lines, the newly inserted sequences typically underwent rapid transcriptional gene silencing, but they lacked cytosine methylation even after many cell divisions. L1 reporter expression was reversible and oscillated frequently. Silenced or variegated reporter expression was strongly and uniformly reactivated by treatment with inhibitors of histone deacetylation, revealing the mechanism for their silencing. By contrast, de novo integrants retrotransposed by L1 in pluripotent mouse embryonic stem (ES) cells underwent rapid silencing by dense cytosine methylation. Similarly, de novo cytosine methylation also was identified at new integrants when studied in several distinct somatic tissues of adult founder mice. Pre-existing L1 elements in cultured human cancer cells were stably silenced by dense cytosine methylation, whereas their transcription modestly increased when cytosine methylation was experimentally reduced in cells lacking DNA methyltransferases DNMT1 and DNMT3b. As a control, reporter genes mobilized by piggyBac (PB), a DNA transposon, revealed relatively stable and robust expression without apparent silencing in both cultured cancer cells and ES cells. CONCLUSIONS:We hypothesize that the de novo methylation marks at newly inserted sequences retrotransposed by L1 in early pre-implantation development are maintained or re-established in adult somatic tissues. By contrast, histone deacetylation reversibly silences L1 reporter insertions that had mobilized at later timepoints in somatic development and differentiation, e.g., in cancer cell lines. We conclude that the cellular contexts of L1 retrotransposition can determine expression or silencing of newly integrated sequences. We propose a model whereby reporter expression from somatic TE insertions reflects the timing, molecular mechanism, epigenetic controls and the genomic, cellular and developmental contexts of their integration.

journal_name

Mob DNA

journal_title

Mobile DNA

authors

Kannan M,Li J,Fritz SE,Husarek KE,Sanford JC,Sullivan TL,Tiwary PK,An W,Boeke JD,Symer DE

doi

10.1186/s13100-017-0091-2

subject

Has Abstract

pub_date

2017-05-10 00:00:00

pages

8

issn

1759-8753

pii

91

journal_volume

8

pub_type

杂志文章
  • Study of VIPER and TATE in kinetoplastids and the evolution of tyrosine recombinase retrotransposons.

    abstract:Background:Kinetoplastids are a flagellated group of protists, including some parasites, such as Trypanosoma and Leishmania species, that can cause diseases in humans and other animals. The genomes of these species enclose a fraction of retrotransposons including VIPER and TATE, two poorly studied transposable elements...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0175-2

    authors: Ribeiro YC,Robe LJ,Veluza DS,Dos Santos CMB,Lopes ALK,Krieger MA,Ludwig A

    更新日期:2019-08-05 00:00:00

  • Evolution of Mutator transposable elements across eukaryotic diversity.

    abstract:Background:Mutator-like elements (MULEs) are a significant superfamily of DNA transposons on account of their: (i) great transpositional activity and propensity for insertion in or near gene sequences, (ii) their consequent high mutagenic capacity, and, (iii) their tendency to acquire host gene fragments. Consequently,...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0153-8

    authors: Dupeyron M,Singh KS,Bass C,Hayward A

    更新日期:2019-03-21 00:00:00

  • Development of a monoclonal antibody specific to the endonuclease domain of the human LINE-1 ORF2 protein.

    abstract:BACKGROUND:LINE-1 (L1) retrotransposons are common occupants of mammalian genomes representing about a fifth of the genetic content. Ongoing L1 retrotransposition in the germ line and somatic tissues has contributed to structural genomic variations and disease-causing mutations in the human genome. L1 mobilization reli...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-014-0029-x

    authors: Sokolowski M,DeFreece CB,Servant G,Kines KJ,deHaro DL,Belancio VP

    更新日期:2014-12-10 00:00:00

  • SeqURE - a new copy-capture based method for sequencing of unknown Retroposition events.

    abstract:BACKGROUND:Retroelements (REs) occupy a significant part of all eukaryotic genomes including humans. The majority of retroelements in the human genome are inactive and unable to retrotranspose. Dozens of active copies are repressed in most normal tissues by various cellular mechanisms. These copies can become active in...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-020-00228-6

    authors: Komkov AY,Urazbakhtin SZ,Saliutina MV,Komech EA,Shelygin YA,Nugmanov GA,Shubin VP,Smirnova AO,Bobrov MY,Tsukanov AS,Snezhkina AV,Kudryavtseva AV,Lebedev YB,Mamedov IZ

    更新日期:2020-12-14 00:00:00

  • Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis.

    abstract:Background:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving loss of motor neurons and having no known cure and uncertain etiology. Several studies have drawn connections between altered retrotransposon expression and ALS. Certain features of the LINE-1 (L1) retrotransposon-encoded ORF1...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-018-0138-z

    authors: Pereira GC,Sanchez L,Schaughency PM,Rubio-Roldán A,Choi JA,Planet E,Batra R,Turelli P,Trono D,Ostrow LW,Ravits J,Kazazian HH,Wheelan SJ,Heras SR,Mayer J,García-Pérez JL,Goodier JL

    更新日期:2018-12-15 00:00:00

  • Transposable element-derived sequences in vertebrate development.

    abstract::Transposable elements (TEs) are major components of all vertebrate genomes that can cause deleterious insertions and genomic instability. However, depending on the specific genomic context of their insertion site, TE sequences can sometimes get positively selected, leading to what are called "exaptation" events. TE se...

    journal_title:Mobile DNA

    pub_type: 杂志文章,评审

    doi:10.1186/s13100-020-00229-5

    authors: Etchegaray E,Naville M,Volff JN,Haftek-Terreau Z

    更新日期:2021-01-06 00:00:00

  • Somatic retrotransposition is infrequent in glioblastomas.

    abstract:BACKGROUND:Gliomas are the most common primary brain tumors in adults. We sought to understand the roles of endogenous transposable elements in these malignancies by identifying evidence of somatic retrotransposition in glioblastomas (GBM). We performed transposon insertion profiling of the active subfamily of Long INt...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-016-0077-5

    authors: Achanta P,Steranka JP,Tang Z,Rodić N,Sharma R,Yang WR,Ma S,Grivainis M,Huang CRL,Schneider AM,Gallia GL,Riggins GJ,Quinones-Hinojosa A,Fenyö D,Boeke JD,Burns KH

    更新日期:2016-11-11 00:00:00

  • Characterization and potential functional significance of human-chimpanzee large INDEL variation.

    abstract:BACKGROUND:Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to ex...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-2-13

    authors: Polavarapu N,Arora G,Mittal VK,McDonald JF

    更新日期:2011-10-25 00:00:00

  • Homologues of bacterial TnpB_IS605 are widespread in diverse eukaryotic transposable elements.

    abstract:BACKGROUND:Bacterial insertion sequences (IS) of IS200/IS605 and IS607 family often encode a transposase (TnpA) and a protein of unknown function, TnpB. RESULTS:Here we report two groups of TnpB-like proteins (Fanzor1 and Fanzor2) that are widespread in diverse eukaryotic transposable elements (TEs), and in large doub...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-4-12

    authors: Bao W,Jurka J

    更新日期:2013-04-01 00:00:00

  • An advanced enrichment method for rare somatic retroelement insertions sequencing.

    abstract:Background:There is increasing evidence that the transpositional activity of retroelements (REs) is not limited to germ line cells, but often occurs in tumor and normal somatic cells. Somatic transpositions were found in several human tissues and are especially typical for the brain. Several computational and experimen...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-018-0136-1

    authors: Komkov AY,Minervina AA,Nugmanov GA,Saliutina MV,Khodosevich KV,Lebedev YB,Mamedov IZ

    更新日期:2018-10-31 00:00:00

  • AluMine: alignment-free method for the discovery of polymorphic Alu element insertions.

    abstract:Background:Recently, alignment-free sequence analysis methods have gained popularity in the field of personal genomics. These methods are based on counting frequencies of short k-mer sequences, thus allowing faster and more robust analysis compared to traditional alignment-based methods. Results:We have created a fast...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0174-3

    authors: Puurand T,Kukuškina V,Pajuste FD,Remm M

    更新日期:2019-07-18 00:00:00

  • Retrotransposon targeting to RNA polymerase III-transcribed genes.

    abstract::Retrotransposons are genetic elements that are similar in structure and life cycle to retroviruses by replicating via an RNA intermediate and inserting into a host genome. The Saccharomyces cerevisiae (S. cerevisiae) Ty1-5 elements are long terminal repeat (LTR) retrotransposons that are members of the Ty1-copia (Pseu...

    journal_title:Mobile DNA

    pub_type: 杂志文章,评审

    doi:10.1186/s13100-018-0119-2

    authors: Cheung S,Manhas S,Measday V

    更新日期:2018-04-23 00:00:00

  • Bacterial group I introns: mobile RNA catalysts.

    abstract::Group I introns are intervening sequences that have invaded tRNA, rRNA and protein coding genes in bacteria and their phages. The ability of group I introns to self-splice from their host transcripts, by acting as ribozymes, potentially renders their insertion into genes phenotypically neutral. Some group I introns ar...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-5-8

    authors: Hausner G,Hafez M,Edgell DR

    更新日期:2014-03-10 00:00:00

  • Extensive exchange of transposable elements in the Drosophila pseudoobscura group.

    abstract:Background:As species diverge, so does their transposable element (TE) content. Within a genome, TE families may eventually become dormant due to host-silencing mechanisms, natural selection and the accumulation of inactive copies. The transmission of active copies from a TE families, both vertically and horizontally b...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-018-0123-6

    authors: Hill T,Betancourt AJ

    更新日期:2018-06-19 00:00:00

  • The diversification of PHIS transposon superfamily in eukaryotes.

    abstract:BACKGROUND:PHIS transposon superfamily belongs to DNA transposons and includes PIF/Harbinger, ISL2EU, and Spy transposon groups. These three groups have similar DDE domain-containing transposases; however, their coding capacity, species distribution, and target site duplications (TSDs) are significantly different. RES...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-015-0043-7

    authors: Han MJ,Xiong CL,Zhang HB,Zhang MQ,Zhang HH,Zhang Z

    更新日期:2015-06-24 00:00:00

  • A call for benchmarking transposable element annotation methods.

    abstract::DNA derived from transposable elements (TEs) constitutes large parts of the genomes of complex eukaryotes, with major impacts not only on genomic research but also on how organisms evolve and function. Although a variety of methods and tools have been developed to detect and annotate TEs, there are as yet no standard ...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-015-0044-6

    authors: Hoen DR,Hickey G,Bourque G,Casacuberta J,Cordaux R,Feschotte C,Fiston-Lavier AS,Hua-Van A,Hubley R,Kapusta A,Lerat E,Maumus F,Pollock DD,Quesneville H,Smit A,Wheeler TJ,Bureau TE,Blanchette M

    更新日期:2015-08-04 00:00:00

  • Differential retention of transposable element-derived sequences in outcrossing Arabidopsis genomes.

    abstract:Background:Transposable elements (TEs) are genomic parasites with major impacts on host genome architecture and host adaptation. A proper evaluation of their evolutionary significance has been hampered by the paucity of short scale phylogenetic comparisons between closely related species. Here, we characterized the dyn...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0171-6

    authors: Legrand S,Caron T,Maumus F,Schvartzman S,Quadrana L,Durand E,Gallina S,Pauwels M,Mazoyer C,Huyghe L,Colot V,Hanikenne M,Castric V

    更新日期:2019-07-17 00:00:00

  • The site-specific integration reaction of Listeria phage A118 integrase, a serine recombinase.

    abstract:UNLABELLED: BACKGROUND:A large subfamily of serine recombinases contains long polypeptide segments appended to the C-terminal end of the conserved catalytic domain. Members of this subfamily often function as phage integrases but also mediate transposition and regulate terminal differentiation processes in eubacteria....

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-4-2

    authors: Mandali S,Dhar G,Avliyakulov NK,Haykinson MJ,Johnson RC

    更新日期:2013-01-03 00:00:00

  • Creation of a novel telomere-cutting endonuclease based on the EN domain of telomere-specific non-long terminal repeat retrotransposon, TRAS1.

    abstract:BACKGROUND:The ends of chromosomes, termed telomeres consist of repetitive DNA. The telomeric sequences shorten with cell division and, when telomeres are critically abbreviated, cells stop proliferating. However, in cancer cells, by the expression of telomerase which elongates telomeres, the cells can continue prolife...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-1-13

    authors: Yoshitake K,Aoyagi H,Fujiwara H

    更新日期:2010-04-01 00:00:00

  • Two large-scale analyses of Ty1 LTR-retrotransposon de novo insertion events indicate that Ty1 targets nucleosomal DNA near the H2A/H2B interface.

    abstract:UNLABELLED: BACKGROUND:Over the years, a number of reports have revealed that Ty1 integration occurs in a 1-kb window upstream of Pol III-transcribed genes with an approximate 80-bp periodicity between each integration hotspot and that this targeting requires active Pol III transcription at the site of integration. Ho...

    journal_title:Mobile DNA

    pub_type: 社论

    doi:10.1186/1759-8753-3-22

    authors: Bridier-Nahmias A,Lesage P

    更新日期:2012-12-17 00:00:00

  • Sex and the TEs: transposable elements in sexual development and function in animals.

    abstract::Transposable elements are endogenous DNA sequences able to integrate into and multiply within genomes. They constitute a major source of genetic innovations, as they can not only rearrange genomes but also spread ready-to-use regulatory sequences able to modify host gene expression, and even can give birth to new host...

    journal_title:Mobile DNA

    pub_type: 杂志文章,评审

    doi:10.1186/s13100-019-0185-0

    authors: Dechaud C,Volff JN,Schartl M,Naville M

    更新日期:2019-11-03 00:00:00

  • flam piRNA precursors channel from the nucleus to the cytoplasm in a temporally regulated manner along Drosophila oogenesis.

    abstract:Background:PIWI-interacting RNAs (piRNAs) are the effectors of transposable element silencing in the reproductive apparatus. In Drosophila ovarian somatic cells, piRNAs arise from long RNA precursors presumably processed within cytoplasmic Yb-bodies. Results:Here we show that the nucleo-cytoplasmic traffic of piRNA pr...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0170-7

    authors: Dennis C,Brasset E,Vaury C

    更新日期:2019-07-06 00:00:00

  • LTRsift: a graphical user interface for semi-automatic classification and postprocessing of de novo detected LTR retrotransposons.

    abstract:UNLABELLED: BACKGROUND:Long terminal repeat (LTR) retrotransposons are a class of eukaryotic mobile elements characterized by a distinctive sequence similarity-based structure. Hence they are well suited for computational identification. Current software allows for a comprehensive genome-wide de novo detection of such...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-3-18

    authors: Steinbiss S,Kastens S,Kurtz S

    更新日期:2012-11-07 00:00:00

  • Pinpointing the vesper bat transposon revolution using the Miniopterus natalensis genome.

    abstract:BACKGROUND:Around 40 million years ago DNA transposons began accumulating in an ancestor of bats in the family Vespertilionidae. Since that time, Class II transposons have been continuously reinvading and accumulating in vespertilionid genomes at a rate that is unprecedented in mammals. Miniopterus (Miniopteridae), a g...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-016-0071-y

    authors: Platt RN 2nd,Mangum SF,Ray DA

    更新日期:2016-07-22 00:00:00

  • Mobile genetic elements and genome evolution 2014.

    abstract::The Mobile Genetic Elements and Genome Evolution conference was hosted by Keystone Symposia in Santa Fe, NM USA, 9 March through 14 March 2014. The goal of this conference was to bring together scientists from around the world who study transposable elements in diverse organisms and researchers who study the impact th...

    journal_title:Mobile DNA

    pub_type:

    doi:10.1186/1759-8753-5-26

    authors: Singh PK,Bourque G,Craig NL,Dubnau JT,Feschotte C,Flasch DA,Gunderson KL,Malik HS,Moran JV,Peters JE,Slotkin RK,Levin HL

    更新日期:2014-11-18 00:00:00

  • Protein-DNA interactions define the mechanistic aspects of circle formation and insertion reactions in IS2 transposition.

    abstract:BACKGROUND:Transposition in IS3, IS30, IS21 and IS256 insertion sequence (IS) families utilizes an unconventional two-step pathway. A figure-of-eight intermediate in Step I, from asymmetric single-strand cleavage and joining reactions, is converted into a double-stranded minicircle whose junction (the abutted left and ...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-3-1

    authors: Lewis LA,Astatke M,Umekubo PT,Alvi S,Saby R,Afrose J,Oliveira PH,Monteiro GA,Prazeres DM

    更新日期:2012-01-26 00:00:00

  • Highly diverse chromoviruses of Beta vulgaris are classified by chromodomains and chromosomal integration.

    abstract:BACKGROUND:Chromoviruses are one of the three genera of Ty3-gypsy long terminal repeat (LTR) retrotransposons, and are present in high copy numbers in plant genomes. They are widely distributed within the plant kingdom, with representatives even in lower plants such as green and red algae. Their hallmark is the presenc...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-4-8

    authors: Weber B,Heitkam T,Holtgräwe D,Weisshaar B,Minoche AE,Dohm JC,Himmelbauer H,Schmidt T

    更新日期:2013-03-01 00:00:00

  • Human transposons are an abundant supply of transcription factor binding sites and promoter activities in breast cancer cell lines.

    abstract:Background:Transposable elements (TE) are commonly regarded as "junk DNA" with no apparent regulatory roles in the human genome. However, a growing body of evidence demonstrates that some TEs exhibit regulatory activities in a range of biological pathways and diseases, with notable examples in bile metabolism and innat...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/s13100-019-0158-3

    authors: Jiang JC,Upton KR

    更新日期:2019-04-27 00:00:00

  • Alu expression in human cell lines and their retrotranspositional potential.

    abstract:BACKGROUND:The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as 'source elements' can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous ge...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-3-11

    authors: Oler AJ,Traina-Dorge S,Derbes RS,Canella D,Cairns BR,Roy-Engel AM

    更新日期:2012-06-20 00:00:00

  • Cell type-specific termination of transcription by transposable element sequences.

    abstract:UNLABELLED: BACKGROUND:Transposable elements (TEs) encode sequences necessary for their own transposition, including signals required for the termination of transcription. TE sequences within the introns of human genes show an antisense orientation bias, which has been proposed to reflect selection against TE sequence...

    journal_title:Mobile DNA

    pub_type: 杂志文章

    doi:10.1186/1759-8753-3-15

    authors: Conley AB,Jordan IK

    更新日期:2012-09-30 00:00:00