Research banner for An Lab showing people laying on the ground spelling out LINE1
Regulation and Function of LINE-1 Retrotransposons in Development and Disease

Welcome to the Laboratory of Dr. Wenfeng An. The An lab studies “jumping genes,” which are DNA sequences that can move from one location to another within the genome. These genes are extremely abundant and make up about 50% of the human genome. Our lab focuses on a specific class of jumping genes, the long interspersed element type 1 (LINE-1; L1 for short).

Research Interest

What is LINE-1 or L1? Long interspersed elements (LINEs) are common components of mammalian genomes. The human genome contains over 500,000 LINE-1 (L1) copies, most of which are 5' truncated. It is estimated that up to 100 L1s are active in the average diploid human genome, whereas ~3000 are potentially active in a diploid mouse genome. Go to Recommended Readings to learn more about these fascinating elements.

Genetic and Epigenetic Regulation of LINE-1 Retrotransposons

  • L1 replicates exclusively inside individual cells, involving steps such as transcription, translation, target-primed reverse transcription and integration. Using mammalian cell culture and transgenic mouse as primary systems, we are interested in dissecting mechanisms of L1 retrotransposition, especially host factors involved in genetic and epigenetic regulation of L1 activity and evolutionary dynamics.

Functional Impacts of LINE-1 retrotransposons

  • L1 is the only active autonomous transposable element in the human genome and it has been replicating in mammals since before the mammalian radiation. We are interested in developing novel mouse models and using them to investigate the impacts of L1 retrotransposition on genomic structure and function. We are particularly interested in the timing of L1 retrotransposition and the corresponding mutational burden during animal development and cancer progression.
More about An Lab
News and Updates
HeLa cells under microscope

[2024] Jeniffer Atim joins TeamLINE1. Welcome!

[2024] Kick off the New Year with a bioRxiv preprint from TeamLINE1: "!"

[2023] Dr. An receives a pilot grant from Sanford Research.

[2023] Heather Collazo joins TeamLINE1. Welcome!

[2022] Grace Nielsen receives the Joseph F. Nelson Summer Research Scholarship.

[2022] Jada Tschetter receives the Schultz-Werth Award.

[2022] Jacob Devine is accepted into University of South Dakota MD Program.

[2021] Lisa Wipf is featured by "news@SDState". Good job, Lisa!

[2021] First bioRxiv preprint from TeamLINE1: ""!

[2021] Raj Naldini joins TeamLINE1. Welcome!

[2021] Dr. An receives Ƶ F. O. Butler Award for Excellence in Research.

[2020] Karabi Saha joins our Ph.D. program. Welcome!

[2020] Lingqi Kong passes his Ph.D. final oral exam. Congrats!

[2020] Partha Saha passes his Ph.D. final oral exam. Congrats!

[2019] Dr. An receives an R03 grant from .

[2019] Both Mason and Chase are accepted into University of South Dakota M.D. Program.

[2019] Heather Collazo joins us this summer as a fellow of the FAST REEU program.

[2019] Trenton LaCanne receives the Joseph F. Nelson Summer Research Scholarship.

[2019] Read our review "Recently mobilized transposons in the human genome" and collaborative work "".

[2018] Dr. An receives an R15 AREA grant from .

[2018] Chase Habben receives the Schultz-Werth Paper Award.

[2018] Partha Saha receives Sigma Xi Graduate Proposal Competition 2nd Place.

[2018] Simon Newkirk receives Professional Staff Excellence in Scholarly Activity Award.

[2017] Chase Habben receives the Joseph F. Nelson Summer Research Scholarship.

[2017] Mason Jones receives the Schultz-Werth Paper Award.

[2017] Simon's is out. See Commentary and .

[2016] Mason Jones receives the Joseph F. Nelson Summer Research Scholarship.

[2016] Nicole Vanden Berg is accepted into University of Minnesota VetMed Program.

[2016] Dr. An is named the College of Pharmacy Outstanding Researcher.

[2015] Dr. An receives two R21 grants from and .

[2015] Our is now online.

[2014] We are now a member of NIGMS P50 Center for Systems Biology of Retrotransposition.

Publications
  1. Saha K., Nielsen G.I., Nandani R., Zhang Y., Kong L., Ye P., An W. YY1 is a transcriptional activator of the mouse LINE-1 Tf subfamily. Nucleic Acids Res. 2024 Oct 26:gkae949. Online ahead of print. PMID: . DOI: . Posted January 4, 2024 on (initial version)
  2. Kong L., Saha S., Hu Y., Tschetter J.N., Habben C.E., Whitmore L.S., Yao C., Ge X., Ye P., Newkirk S.J., An W. Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity. Mobile DNA, 13 (2022). PMID: . PMCID: . DOI: . Posted December 4, 2021 on (initial version)
  3. Gu Z., Liu Y., Zhang Y., Cao H., Lyu J., Wang X., Wylie A., Newkirk S.J., Jones A.E., Lee M. Jr., Botten G.A., Deng M., Dickerson K.E., Zhang C.C., An W., Abrams J.M. and Xu J. Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia. Nature Genetics, 53:672–682 (2021). PMID: . PMCID: . DOI:
  4. Newkirk S.J., Kong L., Jones M.M., Habben C.E., Dilts V.L., Ye P. and An W. Subfamily-specific quantification of endogenous L1 retrotransposons by droplet digital PCR. Analytical Biochemistry, 601:113779 (2020). PMID: . PMCID: . DOI:
  5. Liu R., Sreenivasan C., Yu H., Sheng Z., Newkirk S.J., An W., Smith D.F., Chen X., Wang D. and Li F. Influenza D virus diverges from its related influenza C virus in the recognition of 9-O-acetylated N-acetyl- or N-glycolyl-neuraminic acid-containing glycan receptors. Virology, 545:16-23 (2020). PMID: . PMCID: . DOI:
  6. Newkirk S.J. and An W. UHRF1: a jack of all trades, and a master epigenetic regulator during spermatogenesis. Biology of Reproduction, 102:1147-1152 (2020). PMID: . PMCID: . DOI:
  7. Ray D.A., Paulat N., An W., Boissinot S., Cordaux R., Kaul T., Freeman B. and Belancio V. The 2019 FASEB Science Research Conference on The Mobile DNA Conference: 25 Years of Discussion and Research, June 23–28, Palm Springs, California, USA. FASEB Journal, 33(11):11625-11628 (2019). PMID: . DOI:
  8. Vazquez B.N., Thackray J.K., Simonet N., Chahar S., Kane-Goldsmith N., Newkirk S.J., Lee S., Xing J., Verzi M.P., An W., Vaquero A., Tischfield J.A. and Serrano L. SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina. Nucleic Acids Research, 47:7870–7885 (2019). PMID: . PMCID: . DOI:
  9. Wang Z., McSwiggin H., Newkirk S.J., Wang Y., Oliver D., Tang C., Lee S., Wang S., Yuan S., Zheng H., Ye P., An W. and Yan W. Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype. Mobile DNA, 10:17 (2019). PMID: . PMCID: . DOI:
  10. Saha P. and An W. Recently Mobilized Transposons in the Human Genome. In: . John Wiley & Sons Ltd, Chichester. (2019). DOI:
  11. Reznik B., Cincotta S.A., Jaszczak R.G., Mateo L.J., Shen J., Cao M., Baskin L., Ye P., An W. and Laird D.J. Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells. Development 146(12):dev171157 (2019). PMID: . PMCID: . DOI:
  12. Kawano K., Doucet A.J., Ueno M., Kariya R., An W., Marzetta F., Kuroki M., Turelli P., Sukegawa S., Okada S., Strebel K., Trono D. and Ariumi Y. HIV-1 Vpr and p21 restrict LINE-1 mobility. Nucleic Acids Research 46:8454–8470 (2018). PMID: . PMCID: . DOI:
  13. Sheng Z., Liu R., Yu J., Ran Z., Newkirk S.J., An W., Li F. and Wang D. Identification and characterization of viral defective RNA genomes in influenza B virus. Journal of General Virology 99(4):475-488 (2018). PMID: . PMCID: . DOI:
  14. Newkirk S.J., Lee S., Grandi F.C., Gaysinskaya V., Rosser J.M., Vanden Berg N., Hogarth C.A., Marchetto MCN, Muotri A.R., Griswold M.D., Ye P., Bortvin A., Gage F.H., Boeke J.D. and An W. Intact piRNA pathway prevents L1 mobilization in male meiosis. Proceedings of the National Academy of Sciences of the United States of America 114:E5635–E5644 (2017). PMID: . PMCID: . DOI: . Commented by: Wang P.J. . Proceedings of the National Academy of Sciences of the United States of America 114:7194–7196 (2017). Highlighted by: Chen C. . Biology of Reproduction 97:335-336 (2017)
  15. Kannan M., Li J., Fritz S.E., Husarek K.E., Sanford J.C., Sullivan T.L., Tiwary P.K., An W., Boeke J.D. and Symer EE. Dynamic silencing of somatic L1 retrotransposon insertions reflects the developmental and cellular contexts of their genomic integration. Mobile DNA 8:8 (2017). PMID: . PMCID: . DOI:
  16. Newkirk S.J. and An W. L1 Regulation in Mouse and Human Germ Cells. in , ed Cristofari G (Springer International Publishing), pp 29-61 (2017). DOI: (PDF )
  17. Kharytonchyk S., King S.R., Ndongmo C.B., Stilger K.L., An W. and Telesnitsky A. Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication. Journal of Molecular Biology. 428:2275–2288 (2016). PMID: . PMCID: . DOI: .
  18. Grandi F.C., Rosser J.M., Newkirk S.J., Yin J., Jiang X., Xing Z., Whitmore L., Bashir S., Ivics Z., Izsvák Z., Ye P., Yu Y.E. and An W. Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites. Genome Research. 25:1135-1146 (2015). PMID: . PMCID: . DOI: .
  19. Grandi F.C. and An W. Non-LTR retrotransposons and microsatellites: Partners in genomic variation. Mobile Genetic Elements. 3:e25674 (2013). PMID: . PMCID: . DOI: .
  20. O'Donnell K.A., An W., Schrum C.T., Wheelan S.J. and Boeke J.D. Controlled insertional mutagenesis using a LINE-1 (ORFeus) gene-trap mouse model. Proceedings of the National Academy of Sciences of the United States of America 110:E2706-13 (2013). PMID: . PMCID: . DOI: .
  21. Xie Y., Mates L., Ivics Z., Izsvák Z., Martin S.L. and An W. Cell division promotes efficient retrotransposition in a stable L1 reporter cell line. Mobile DNA. 4:10 (2013). PMID: . PMCID: . DOI:
  22. Grandi F.C., Rosser J.M. and An W. LINE-1 derived poly(A) microsatellites undergo rapid shortening and create somatic and germline mosaicism in mice. Molecular Biology and Evolution. 30:503-12 (2013). PMID: . PMCID: . DOI: .
  23. Ray D., Hogarth C.A., Evans E.B., An W., Griswold M.D. and Ye P. Experimental validation of Ankrd17 and Anapc10, two novel meiotic genes predicted by computational models in mice. Biology of Reproduction 86(4):102 (2012). PMID: . PMCID: . DOI:
  24. Rosser J.M. and An W. L1 expression and regulation in humans and rodents. . PMID: . PMCID: . 
  25. An W., Dai L., Niewiadomska A.M., Yetil A., O'Donnell K.A., Han J.S. and Boeke J.D. Characterization of a synthetic human LINE-1 retrotransposon ORFeus-Hs. Mobile DNA. 2:2 (2011). PMID: . PMCID: . DOI: .
  26. Xie Y., Rosser J.M., Thompson T.L., Boeke J.D. and An W. Characterization of L1 retrotransposition with high-throughput dual-luciferase assays. Nucleic Acids Research 39, e16 (2011). PMID: . PMCID: . DOI: .
  27. Rosser J.M. and An W. Repeat-induced gene silencing of L1 transgenes is correlated with differential promoter methylation. Gene 456, 15-23 (2010). PMID: . PMCID: . DOI: .
  28. An W., Davis E.S., Thompson T.L., O'Donnell K.A., Lee C-Y and Boeke J.D. Plug and play modular strategies for synthetic retrotransposons. Methods 49, 227-35 (2009). PMID: . PMCID: . DOI: .
  29. Han Y., Lin Y.B., An W., Xu J., Yang H.C., O'Connell K., Dordai D., Boeke J.D., Siliciano J.D. and Siliciano RF. Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe 4, 134-46 (2008). PMID: . PMCID: . DOI: .
  30. An W., Han J.S., Schrum C.M., Maitra A., Koentgen F. and Boeke J.D. Conditional activation of a single-copy L1 transgene in mice by Cre. Genesis 46, 373-83 (2008). PMID: . PMCID: . DOI: .
  31. Boeke J.D., An W., Dai L., Davis E.S., Han, J.S., O'Donnell K.A., Scheifele L.Z. and Wheelan, S.J. . doi:10.1007/978-3-540-74966-0_3. ISBN: 978-3-540-74965-3 (Print) 978-3-540-74966-0 (Online)
  32. An W., Han J.S., Wheelan S.J., Davis E.S., Coombes C.E., Ye P., Triplett C. and Boeke J.D. Active retrotransposition by a synthetic L1 element in mice. Proceedings of the National Academy of Sciences of the United States of America 103, 18662-7 (2006). PMID: . PMCID: . DOI: .
  33. An W. and Boeke J.D. Transposon technology and vertebrate functional genomics. Genome Biology 6, 361 (2005). PMID: . PMCID: . DOI: .
Opportunities

Undergraduate Student

Projects are available for motivated undergraduate students. Will work on independent projects as well as teaming with experienced graduate students and postdocs. Must be committed and have a passion for biomedical research.

Graduate Student

No current openings. Prospective students may submit pre-application inquiry to Dr. An.
Ph.D. Program and Instructions

Meet the Team

Get to know the team of the An Lab

anlab dr an photo
Wenfeng An
Principal Investigator
Nielsen photo
Grace Nielsen
Undergraduate Student
anlab graduate student photo
Jeniffer Atim
Graduate Student
Heather Collazo
Heather Collazo
Graduate Student
Raj photo
Raj Nandani
Graduate Student
Karabi Saha
Graduate Student
Principal Investigator