Genomic, Transcriptional and Epigenetic Variation Due to Retrotransposition

Symer实验室小组-#61550;于2009年迁至俄亥俄州州立大学 综合癌症中心#61550;继续建立 内源性逆转录因子导致广泛的基因组和转录变异 区分经典和野生小鼠品系。这些插入/缺失（indel） 多态性已经在一个公共数据库PolyBrowse中制成表格， 高级生物医学计算中心（ABCC）。&我们 发现更多的证据表明，几乎没有年轻的转座子整合体存在于 经典的近交系小鼠品系存在于与野生品系相同的染色体位置 基因组我们发现了其他新的转录本结构， 小鼠品系直接归因于这些最近整合的转座子中的一些 并在特定的发育时间在特定的组织中以受调节的方式表达 点我们继续识别和表征数千个长 在不同经典和野生型中含有末端重复序列（LTR）反转录转座子多态性 小鼠品系。我们表征了一些多态性LTR反转录转座子的表达， 融合LTR基因转录本在大多数成年小鼠组织中广泛表达。总的来说， 这种表达模式与融合L1基因转录物的表达模式不同。 我们继续对转录本表达进行广泛的统计分析， DNA甲基转移酶亚型细胞，比较基因表达cDNA系列分析 文库标签计数与新获得的外显子微阵列数据。分析显示， 可能的签名基因，其表达与其胞嘧啶甲基化密切相关。 这些基因包括睾丸癌基因、干扰素诱导基因、主要组织相容性基因、 复合物（MHC）基因和金属硫蛋白基因簇的成员。&我们 继续建立在从头L1整合体上建立的表观遗传控制是非常重要的。 在培养的癌细胞中不同（其中存在动态组蛋白尾标记， 乙酰化建立）与体内体组织和小鼠胚胎干细胞（其中 它们经历密集的胞嘧啶甲基化）。

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).