The Symer lab group - Moved in 2009 to The Ohio State University Comprehensive Cancer Center Continued to establish that transposition of endogenous retroelements resulted in extensive genomic and transcriptional variation distinguishing classical and wild mouse strains. These insertion / deletion (indel) polymorphisms have been tabulated in a public database, PolyBrowse, developed in collaboration with Advanced Biomedical Computing Center (ABCC) at NCI-Frederick. We found more evidence that virtually none of the young transposon integrants present in classical inbred mouse strains are present at the same chromosomal locations in wild strain genomes. We found additional 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. We continued to identify and characterize thousands of long terminal repeat (LTR)-containing retrotransposon polymorphisms in different classical and wild 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. We continued extensive statistical analysis of transcript expression from DNA methyltransferase hypomorphic cells, comparing serial analysis of gene expression cDNA library tag counts with newly acquired exon 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. We continued to establish that epigenetic controls set up at de novo L1 integrants are very different in cultured cancer cells (where there are dynamic histone tail marks such as acetylation established) vs. somatic tissues in vivo and in mouse embryonic stem cells (where they undergo dense cytosine methylation).

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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