archives@tulane.edu / These studies make strides in better understanding retroelement L1 expression and regulation at the locus-specific level using a combination of sequencing technologies. A picture is painted demonstrating tissue specific patterns of L1 expression when identified stringently and confidently with our developed EL-Seq approach. As it was also determined that expressed L1s significantly correlate with regions of open chromatin, these tissue-specific patterns of L1 expression are then most likely explained by tissue-specific chromatin architecture. Evidence is also presented here that L1s in tissues respond differently with genomic stresses and perturbations as is seen in the case of aging indicating that the risk associated with L1 damage and mutagenesis is related to cell type and tissue. This is particularly notable when considering the genesis and promotion of age-related somatic diseases like epithelial cancers. L1s are commonly referred to as the dark matter of the genome, but here we illuminate its biology and regulation to better understand L1-associated damage and risk to human health. / 0 / Tiffany Kaul

The reverse flow of genetic information can occur when a special DNA polymerase called Reverse Transcriptase (RT) copies the genetic information in an RNA molecule back into a complementary DNA. One type of RT encoding gene found in bacteria is called a retron element. Recent bacterial genome sequencing projects have revealed many examples of retron RT genes. This gene assignment is based on comparison with a few known retron RT proteins. However, RT proteins are highly diverse in their amino acid sequences, and thus the assigned identity of these RT proteins as retrons in genome databases is questionable. One way to prove that these postulated RTs are indeed from retron elements is to see if they can produce msDNA. Retron RTs are known to synthesize a structurally unique satellite DNA called msDNA in the bacterial cells that contain them. Based on GenBank database matches to a known protein, 7 proteins designated as retron RTs were tested for their ability to synthesize msDNA. Five of these retron RTs did show evidence of producing msDNA and are from very different bacterial hosts. The other 2 RT proteins did not show any evidence that they produce msDNA.

Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ~100 remain retrotransposon competent (RC-L1) and retrotranspose through RNA intermediates to different locations of the genome. It is well established that L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt loci (e.g. gene structure) in ways that lead to human disease, and activities of L1 si/piRNA, ORF1 and ORF2 proteins are implicated in the etiology and progression of human diseases such as in breast and colon cancer (Miki et al., 1992; Ohms et al., 2014). Despite these implications, very little is known about pharmacological molecules that inhibit and reverse L1’s harmful effects. The clinical utility of L1 as a player in tumorigenesis and as a biomarker for disease initiation and progression is not thoroughly understood. In this review, we analyzed the life cycle of L1, its roles in disease initiation and progression, clinical utilities and potential as a pharmacological target and a biomarker for the diagnosis and treatment of human diseases, such as cancer.

Thesis (M.Sc.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2008/01/16). Includes bibliographical references.

Thesis (Ph.D. in Biophysics & Genetics, Human Medical Genetics Program) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 123-147). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;