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Articles 1 - 4 of 4
Full-Text Articles in Medicine and Health Sciences
Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram Gayatri
Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram Gayatri
Dissertations & Theses (Open Access)
A limited pool of proteins attains vast functional repertoire due to posttranslational modifications (PTMs). Arginine methylation is a common posttranslational modification, which is catalyzed by a family of nine protein arginine methyltransferases or PRMTs. These enzymes deposit one or two methyl groups to the nitrogen atoms of arginine side-chains. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified, and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed. Here we describe the …
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations & Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …
Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell
Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell
Dissertations & Theses (Open Access)
Rac1 is a small, guanine-nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate actin-mediated motility, migration, and adhesion. Plasma membrane (PM) localization is essential for its biological activity. Rac1 PM targeting is directed by a C-terminal membrane anchor that encompasses a geranylgeranyl-cysteine-methyl-ester, palmitoyl, and a polybasic domain (PBD) of contiguous lysine and arginine residues. Using high-resolution imaging combined with spatial mapping analysis, I found that Rac1 forms nanoclusters on the PM. Cycling between the GTP- and GDP-bound states, Rac1 forms nanoclusters that are non-overlapping, consequently undergoing guanine nucleotide-dependent spatial segregation. I further found that …
Investigating The Impact Of Intragenic Dna Methylation On Gene Expression, And The Clinical Implications On Tumor Cells And Associated Stroma, Michael Mcguire
Investigating The Impact Of Intragenic Dna Methylation On Gene Expression, And The Clinical Implications On Tumor Cells And Associated Stroma, Michael Mcguire
Dissertations & Theses (Open Access)
Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions; however, integrated non-promoter DNA methylation and gene expression analyses across a wide number of tumor types and corresponding normal tissues have not been performed. Through integrated analysis of gene expression and DNA methylation profiles, we uncovered an enrichment of DNA methylation sites within the gene body and 3’UTR in which DNA methylation is strongly positively correlated with gene expression. We examined 32 tumor types and identified 57 …