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


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.




Mobile DNA


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




Has Abstract


2017-05-10 00:00:00










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  • 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,...

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    journal_title:Mobile DNA

    pub_type: 杂志文章


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

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  • 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...

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    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

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    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...

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    pub_type: 杂志文章,评审


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    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


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

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    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...

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    authors: Bao W,Jurka J

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

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    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...

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

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    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


    authors: Cheung S,Manhas S,Measday V

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    authors: Hausner G,Hafez M,Edgell DR

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    pub_type: 杂志文章


    authors: Hill T,Betancourt AJ

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Mobile DNA

    pub_type: 杂志文章


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    journal_title:Mobile DNA

    pub_type: 社论


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    journal_title:Mobile DNA

    pub_type: 杂志文章,评审


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    journal_title:Mobile DNA

    pub_type: 杂志文章


    authors: Dennis C,Brasset E,Vaury C

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    authors: Steinbiss S,Kastens S,Kurtz S

    更新日期:2012-11-07 00:00:00

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    journal_title:Mobile DNA

    pub_type: 杂志文章


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

    更新日期:2016-07-22 00:00:00

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    journal_title:Mobile DNA



    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

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    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

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    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.

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    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.

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    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

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    journal_title:Mobile DNA

    pub_type: 杂志文章


    authors: Conley AB,Jordan IK

    更新日期:2012-09-30 00:00:00