Date of Award


Degree Type


Degree Name

Master of Science (MS)




While 10-15% of the human genome is composed of heterochromatic DNA, these regions are not included in the completed genome sequence. The short arm of chromosome 21 (HC21p) serves as a model for understanding the structure and function of heterochromatin. LINE-1 (L1) retrotransposons are underrepresented in heterochromatin, including HC21p, and have not been extensively studied in these regions. However, there are disproportionately more full length L1s on HC21p than in euchromatic genomic regions. Decreased DNA methylation in the promoters of these L1s on HC21p may allow them to facilitate heterochromatin formation, which would be analogous to their proposed role in X chromosome inactivation. Using bisulfite sequencing PCR on both chromosome-specific hybrid cell lines and leukocytes, I found that overall methylation of four specific L1s on HC21p was substantially lower than control L1 loci located in euchromatic regions. This trend was also present for four critical CpG sites in the L1 promoter that have been specifically implicated in the suppression of L1 expression. I propose a model wherein decreased L1 promoter methylation promotes heterochromatin formation by intrachromosomal interactions and transient bidirectional expression.

Additionally, due to evidence that some L1s become hypomethylated in cancer cells, a limited number of HC21p L1 loci were analyzed in a small number of prostate cancer cell lines to determine if changes in methylation at those loci could be relevant to the development of a cancer biomarker. I found that the L1s on HC21p were generally less methylated in cancer versus normal cell lines and differed between loci at different tumor stages. This supports the hypothesis that changes in methylation of a variety of specific L1 loci may be sensitive biomarkers for both cancer detection and prognosis.

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