Henry L. Levin, Ph.D.
Section on Eukaryotic Transposable Elements
Retrotransposons as Models for the Replication of Retroviruses
Inherently mutagenic, the integration of retroviral and retrotransposon DNA is responsible for many pathologies, including malignancy. In particular, the integration of HIV-1 shows a significant preference for actively transcribed genes, a preference that is dependent on the host factor LEDGF (lens epithelium–derived growth factor). Similarly, the insertion of murine leukemia virus shows a strong preference for sites within 5 kb of transcription initiation. An understanding of the mechanisms responsible for targeted integration could lead to new approaches to block the replication of HIV-1. Given that the use of an murine leukemia virus (MLV)–based vector in infants with severe immunodeficiency resulted in integration events at a known protoncogene gene as well as the induction of leukemia in patients, another key motivation for the study of integration preferences is to improve the safety of retrovirus vectors used in gene therapy.
Dr. Henry Levin heads the Section on Eukaryotic Transposable Elements in NICHD, which analyzes LTR retrotransposons as a model for the replication of retroviruses. Over the past 25 years Dr. Levin’s studies of LTR retrotransposons in fission yeast identified mechanistic details of particle formation, reverse transcription, and integration. Recently, the laboratory demonstrated that Tf1 integration occurs primarily at promoters and used ultra-high throughput sequencing to generate a saturated map of sites targeted by Tf1. Research projects in the Levin lab also include studies of HIV-1 integration and health implications of human retrotransposons. Dr. Levin has organized several conferences and symposia on transposon biology and retrovirus replication. Within the last year he has been a principal co-organizer for the ASM sponsored International Conference on Mobile DNA and the Retrovirus Meeting held at the Cold Spring Harbor Laboratories. In 2009 he edited a special issue of the journal Methods on Transposon Technology and in 2011 he published a review of Transposon Biology in Nature Reviews Genetics. In 2011 Dr. Levin received the NIH Graduate Student Outstanding Mentor Award.
Chatterjee AG, Esnault C, Guo Y, Hung S, McQueen PG, Levin HL. Serial number tagging reveals a prominent sequence preference of retrotransposon integration. Nucleic Acids Res. 2014;42(13):8449-60.
Guo Y, Park JM, Cui B, Humes E, Gangadharan S, Hung S, FitzGerald PC, Hoe KL, Grewal SI, Craig NL, Levin HL. Integration profiling of gene function with dense maps of transposon integration. Genetics. 2013;195(2):599-609.
Feng G, Leem YE, Levin HL. Transposon integration enhances expression of stress response genes. Nucleic Acids Res. 2013;41(2):775-89.
Singh PK, Plumb MR, Ferris AL, Iben JR, Wu X, Fadel HJ, Luke BT, Esnault C, Poeschla EM, Hughes SH, Kvaratskhelia M, Levin HL. LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes. Genes Dev. 2015;29(21):2287-97.
Rai SK, Sangesland M, Lee M Jr, Esnault C, Cui Y, Chatterjee AG, Levin HL. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes. PLoS Genet. 2017;13(12):e1006775.
Related Scientific Focus Areas
Genetics and Genomics
Microbiology and Infectious Diseases
Molecular Biology and Biochemistry
This page was last updated on September 7th, 2018