Megan Guntrum

Dr. Tamara Davis

Biology

Methylation and hydroxymethylation patterns in the mouse IG-DMR

 

Genomic imprinting is a form of epigenetic regulation of gene expression in mammals.  For most genes, both the maternal and paternal alleles are expressed.  However, imprinted genes have one allele marked early in development, depending on their parental origin, through either DNA methylation or histone modification.  These markings, which are differentially distributed, cause one allele to be expressed.  So far approximately 150 imprinted genes have been discovered in humans and mice.  The imprinting of these genes is necessary for proper growth and development, and multiple disorders are known to develop when imprinted genes are improperly expressed.  Research into the mechanisms and patterns of DNA methylation is necessary to better understand and develop treatments for these human disorders.

One of the forms of genomic imprinting, DNA methylation, involves the addition of a methyl group to the cytosine at CpG dinucleotides on both complementary strands.  99% of mammalian DNA is symmetrically methylated, however previous research showed an unusually high percentage of asymmetrical methylation at the Dlk1 differentially methylated region (Dlk1-DMR) in mice.  This region is methylated during embryonic development and correlates with more variable DNA methylation patterns.  Our current study is analyzing a more stably methylated region, intergenic DMR (IG-DMR), which is methylated during spermatogenesis.  We hypothesize that this region will be mostly symmetrically methylated because regions that are methylated earlier in development are correlated with more stable methylation patterns.  In addition, the percentage of 5-hydroxymethylcytosine (5-hmc) will be analyzed in the IG-DMR, as it is an intermediate in DNA demethylation and may provide insight into the mechanism responsible for DNA methylation loss over time.