Relationship between repetitive sequence environment and mammalian gene expression

Repetitive sequences have been reported to influence the expression of individual genes. Two models for gene expression are used in this study: Housekeeping genes, which are highly expressed and monoallelic genes, which are expressed from a single allele while the other allele is silenced. Housekeeping genes require open, euchromatic environments free of heterochromatin in order to achieve high levels of gene expression. Autosome- and X-inactivated genes must establish and maintain allele-specific chromatin structures conducive to monoallelic gene silencing. The purpose of this study is to identify broad advantages to the presence of repetitive elements in mammalian genomes, specifically with regard to their role in regulating expression of these two classes of genes. Using a bioinformatics approach, this study aims to elucidate the impact that long-range sequence environment has on gene expression. The genomic distributions of about thirty families of mammalian repetitive elements are examined and compared to the distributions of the various gene classes. Those correlations are then used as covariates in unsupervised clustering algorithms to describe previously overlooked subpopulations within the gene classes.;This study shows that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. These covariates are then used to predict higher gene expression, and demonstrates the importance of repeat sequence environment in distinguishing housekeeping genes.;The second part of this study shows that all three categories of monoallelically expressed genes contain subpopulations that can be distinguished by high concentrations of flanking LINE-1 elements or higher concentrations of flanking SINE elements, in both humans and mice. The absence of monoallelically expressed genes displaying both "high LINE" and "high SINE" characteristics suggests that SINEs and LINEs provide alternative but mutually incompatible frameworks for monoallelic gene expression. Furthermore, this study shows that both the "high-LINE" and "high-SINE" groups of monoallelic genes were associated with distinct transcription factor binding sites.