The Symer lab group - - Found that transposition of endogenous retroelements resulted in extensive genomic and transcriptional variation distinguishing classical mouse strains, exceeding that from single nucleotide polymorphisms (SNPs). These insertion / deletion (indel) polymorphisms have been made public via a new website, PolyBrowse, developed in collaboration with Advanced Biomedical Computing Center (ABCC) at NCI-Frederick. We found increased transposon indels in brain-associated genes, but significantly reduced indel polymorphisms on the X chromosome. We found that virtually none of the young transposon integrants present in classical inbred mouse strains are present in wild strain genomes. - Identified numerous novel transcript structures distinguishing mouse strains that are attributable directly to some of these recently integrated transposons and are expressed in a regulated fashion in specific tissues at specific developmental time points. - Developed a new molecular technique to identify newly mobilized endogenous transposons, and showed that human L1 elements actively move in cultured cancer cell lines within a few weeks. These results show that transposons can alter the normal mammalian genome, and gene expression profiles, dramatically and in real time. - Found that a disproportionate number of dimorphic endogenous transposons in mouse strains are located in or near genes expressed in brain. Numerous novel transcript structures, attributable directly to recent transposon integrants, are specifically expressed in brain and/or testis. Most endogenous transposons are expressed in only certain tissues, typically early in development, such as brain and testis. - Identified thousands of long terminal repeat (LTR)-containing retrotransposon polymorphisms in different classical mouse strains. We characterized expression of some polymorphic LTR retrotransposons and found extensive expression of fusion LTR-gene transcripts in most adult mouse tissues. In general, this pattern of expression is distinct from that for fusion L1-gene transcripts. - Found sense and antisense 25 nt RNAs from mouse L1 retrotransposons in mouse testis, suggesting that small RNAs are generated and may play a role in control of transposon expression and movement. - Found preliminary evidence for expression of micro RNAs exclusively as fusion transposon-microRNA transcripts. This result supports a new way by which microRNA expression can be established and regulated in cells. - Conducted extensive statistical analysis of transcript expression from DNA methyltransferase hypomorphic cells, comparing serial analysis of gene expression cDNA library tag counts with microarray data. This analysis revealed a set of possible signature genes whose expression is closely linked to their cytosine methylation. These include cancer testis genes, interferon-inducibile genes, major histocompatibility complex (MHC) genes, and members of the metallothionein gene cluster. - Found that epigenetic controls of de novo L1 integrants are very different in tissue culture cells (where there are dynamic histone tail marks such as acetylation established) vs. somatic tissues in vivo (where they undergo dense cytosine methylation).
| Agrawal, Yuri; Koch, Wayne M; Xiao, Weihong et al. (2008) Oral human papillomavirus infection before and after treatment for human papillomavirus 16-positive and human papillomavirus 16-negative head and neck squamous cell carcinoma. Clin Cancer Res 14:7143-50 |
| Akagi, Keiko; Li, Jingfeng; Stephens, Robert M et al. (2008) Extensive variation between inbred mouse strains due to endogenous L1 retrotransposition. Genome Res 18:869-80 |
