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Research Interests
Genetic and epigenetic regulation of mammalian L1
retrotransposons and functional genomics
Research Summary
Long interspersed elements type 1
(LINE-1 or L1) are a common component of mammalian genomes and a
major driver of mammalian genome evolution. More than 500,000
copies of L1 are present in the human genome, and up to 100 L1s
remain active. The expression of these “jumping genes”
is developmentally regulated and involves piRNA and DNA
methylation. Recent work has indicated a potential role of L1 in
mammalian meiosis and in contributing to individual somatic
mosaicism, especially in the brain. Two areas of L1 research are
the focus of our laboratory.
(1) Genetic and epigenetic regulation of L1
retrotransposons. L1 replicates exclusively within cells, involving
steps such as transcription, translation, target-primed reverse
transcription and integration. Using mammalian cell culture and
transgenic mice as primary systems, we are interested in dissecting
mechanisms of L1 retrotransposition, especially host factors
involved in genetic and epigenetic regulation of L1 activity at
both transcriptional and posttranscriptional stages.
(2) Functional genomic studies in mice using L1. L1 can randomly insert new copies of itself throughout the genome by retrotransposition. This feature makes it an attractive tool for functional genomic studies in an important model organism for human diseases, the mouse. We are interested in developing an insertional mutagenesis system based on a synthetic L1, ORFeus, for forward genetic screens.
Research Publications
2005-2009
An, W., E.S. Davis, T.L. Thompson, K.A. O'Donnell, C.Y. Lee, and J.D. Boeke, Plug and play modular strategies for synthetic retrotransposons. Methods, in press (2009).
Han, Y., Lin, Y.B., An, W., Xu, J., Yang, H.C., O’Connell, K., Dordail, D., Boeke, J.D., Siliciano, J.D., & Siliciano R.F. Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe. 4, 134-46 (2008).
An, W., Han, J.S., Schrum, C.M., Maitra, A., Koentgen, F. & Boeke, J.D. Conditional activation of a single-copy L1 transgene in mice by Cre. Genesis 46, 373-83 (2008).
An, W., Han, J.S., Wheelan, S.J., Davis, E.S.,
Coombes, C.E., Ye, P., Triplett, C. & Boeke, J.D. Active
retrotransposition by a synthetic L1 element in mice. Proc Natl
Acad Sci U S A 103, 18662-7 (2006).