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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25633

Title: Epigenetic Basis for Heterogeneity in VCAM-1 Gene Expression Patterns in Cytokine Activated Vascular Endothelium
Authors: Jamal, Alisha Noorin
Advisor: Marsden, Philip A.
Department: Laboratory Medicine and Pathobiology
Keywords: Pathology
Biology
Vascular Endothelium
Epigenetics
VCAM-1
Issue Date: 1-Jan-2011
Abstract: Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-activated protein present on endothelial cells (ECs). Our laboratory has provided evidence that DNA methylation, a mark associated with gene silencing, is fundamental for regulating VCAM-1 expression. First, we showed that RNA polymerase II, preferentially associates with VCAM-1 hypomethylated alleles. This finding was confirmed using fluorescence-activated cell sorting (FACS) to sort populations of cytokine-activated ECs with high vs. low cell surface VCAM-1 expression. We found that ECs with high VCAM-1 expression were hypomethylated at the promoter. We then went on to show that populations of cells generated from single ECs exhibit differential VCAM-1 methylation from one another, and from the original founder population. Intriguingly, our data shows that VCAM-1 mRNA levels differ between the clones, and correlate with the observed differences in DNA methylation. Taken together, this data provides exciting evidence that DNA methylation is important in the regulation of VCAM-1 gene expression.
URI: http://hdl.handle.net/1807/25633
Appears in Collections:Master
Department of Laboratory Medicine and Pathobiology - Master theses

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