Genomic, Transcriptional and Epigenetic Variation Due to Retrotransposition

2009年搬到俄亥俄州立大学综合癌症中心的Smer实验室小组继续证实，内源性逆转录元件的转位导致了区分经典小鼠和野生小鼠品系的广泛基因组和转录差异。这些插入/缺失(INDEL)多态已被列在公共数据库PolyBrowse中，该数据库与NCI-Frederick的先进生物医学计算中心(ABCC)合作开发。我们发现更多的证据表明，在经典近交系小鼠基因组中，几乎没有一个年轻的转座子整合子存在于野生品系基因组的相同染色体位置。我们发现了其他新颖的转录本结构，以区分小鼠品系，这些转座子直接归因于一些最近整合的转座子，并在特定发育时间点的特定组织中以受调控的方式表达。我们继续在不同的经典和野生小鼠品系中鉴定和表征数以千计的含有长末端重复序列的反转录转座子多态。我们鉴定了一些多态的LTR反转录转座子的表达，并发现融合的LTR基因转录本在大多数成年小鼠组织中广泛表达。一般来说，这种表达模式不同于融合的L1基因转录本。我们继续对DNA甲基转移酶亚型细胞的转录表达进行了广泛的统计分析，将基因表达cDNA库标签计数的系列分析与新获得的外显子微阵列数据进行了比较。这项分析揭示了一组可能的标志性基因，它们的表达与胞嘧啶甲基化密切相关。这些基因包括癌症睾丸基因、干扰素诱导胆汁基因、主要组织相容性复合体(MHC)基因和金属硫蛋白基因簇的成员。我们继续证实，在培养的癌细胞(存在动态的组蛋白尾部标记，如乙酰化)与体内的体细胞组织和小鼠胚胎干细胞(它们在那里经历密集的胞嘧啶甲基化)中，在从头开始L1整合体建立的表观遗传学控制非常不同。

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).