Biology of LINE-1 retrotransposons

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Biology of LINE-1 retrotransposons

Dr. Jose Luis García Pérez, Dra. Sara R. Heras

Scientific interest areas

More than 50% of the human genome has been generated by the activity of mobile DNA elements or Transposable Elements (TEs). TEs are pieces of mobile DNA that are mobilized in our genome at the germline and somatic levels. As pieces of mobile DNA, TEs represent the major force in the generation of genomic variability among humans.

Within the TEs present in the human genome, at present only retrotransposons of the non-LTR class are currently active in our genome. Active non-LTR retrotransposons in the human genome includes LINE-1 or L1 elements and SINEs Alu ans SVA. Despite its prevalence in our genome, only a limited number of L1, Alu and SVA elements are able to currently move in our genome, and are termed retrotransposition competent. L1 elements are autonomous retrotransposons that encoded the enzymatic machinery required to mediate their mobilization. On the other hand, Alu and SVA elements likely use the proteins encoded by active L1s to mediate their mobilization in trans. In sum, a third of our genome has been generated by the activity of a single type of mobile DNA: LINE-1 or L1 elements.

Besides their potential to generate genomic variability, as a piece of DNA that inserts in our genome, new retrotransposition events have been associated with a significant number of human diseases. Due to their random insertion in our genome, L1 mediated processes have been shown to generate a wide range of human diseases (cancer, hemophilia, muscular dystrophy, etc). Indeed, L1 mediated processes can impact and alter the locus where they insert in a myriad of ways (from simple insertional mutagens to inducing severe genomic alterations at the insertion site). Although TEs were described in the 50´s, little is known about their germline and somatic genomic impact or their regulation in our genome.

Our lab studies how mobile DNA elements (mostly L1 elements) impact the genome of stem cells, as most de novo insertion in man seems to accumulate during early embryogenesis. In addition, our lab also studies their impact in selected somatic tissues and in certain pathologies as cancer and Fanconi Anemia. Finally, our lab is also interested in identifying cellular host factors that regulate retrotransposition and how L1 elements induce variability during human embryogenesis.

Research areas

  • Impact and genomic mosaicism induced by the human LINE-1 retrotransposon. We are currently determining the mutagenic potential of de novo L1 retrotransposition events in somatic human tissues. To do that, we use human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs) and somatic tissues as a source of somatic stem cells.
  • LINE-1 and Fanconi Anemia. We are currently characterizing the impact of L1 mobilization events in cell lines isolated from patients affected with Fanconi Anemia. The main goal is to shed light in the molecular basis of this fatal human disease.
  • LINE-1 and cancer. We are generating a census of expressed TEs in human tumors, using a cell based L1 retrotransposition assay to determine if L1 activity is different among human tumors. The main goal is to determine if L1 expression/activity is a marker of disease progression. In addition, we are developing deep sequencing approaches to determine the frequency of L1 mobilization in human tumors.
  • L1 activity during human early embryogenesis. We are determining the level and types of L1s expressed in human embryos and in germ cells, as we and others previously demonstrated that most de novo L1 retrotransposition events are accumulated during early human embryogenesis. In addition, and using deep sequencing, we are testing at the single cell level if endogenous L1s are retrotransposing in human embryos.
  • Epigenetic control of LINE-1 retrotransposons. We are currently characterizing host factors that mediated the epigenetic silencing of new L1 insertions in pluripotent cells. In addition, we are testing if L1 retrotransposition events can acts as “epimutagens” in an array of pluripotent cells.

Technology platforms

    • Roche 454 deep sequencing
    • Reprogramming to iPSCs
    • Real Time PCR


    • Howard Hughes Medical Institute.
    • European Research Council (ERC)
    • Marie Curie Actions (EU, 7PM).
    • Instituto de Salud Carlos III.
    • Consejería de Salud Junta de Andalucia.
    • Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía.

Research group patents

Application Number: P200101817
Priority Date: June 2001
Title: LINE mobile retroelements with Rnase H enzymatic activity and their use.
Authors (1st Surname, Initials): Olivares, M.; García-Pérez, J.L.; Thomas, M.C.; López, M.C.
Applicant: CSIC, Spain.

Additional information

Dr. Garcia-Perez is an International Early Career Scientist from the Howard Hughes Medical Institute ( Dr. Garcia-Perez is an Associated Principal Investigator of the European Network EuroSystem (2010-2013). The EU Framework 7, in the activity area HEALTH, funds Eurosystem. Eurosystem enroll some of Europe’s top stem cell research groups to further increase new knowledge in stem cell biology (

Dr. Garcia-Perez is a lecturer at the Official Master’s Degree in Immunology at the UGR:

Selected publications

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