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Elizabeth Sergison

Elizabeth is originally from New Jersey and received her B.A. in biological sciences from Mount Holyoke College in 2011. At Mount Holyoke, she studied genetic diversity in heirloom versus modern tomato varieties in the lab of Dr. Amy Frary. Previously, she worked in the lab of Dr. Stephen Glatt at SUNY Upstate Medical School. She studied the effect of the rs1076560 single nucleotide polymorphism on alternative splicing of DRD2, which is associated with risk for schizophrenia. In her spare time, Elizabeth enjoys baking and playing with her two kittens.

Research Interests
Chromatin architecture, SNPs in intergenic regions, epigenetics, cancer genetics

Research Summary
Deregulated expression of the oncogene c-MYC is present in 70% of all cancers; overexpression results in uncontrolled cell proliferation and cellular transformation. c-MYC is located within a large 3 Mb gene-free region in the human genome. Genome-wide association studies have found single nucleotide polymorphisms (SNPs) associated with increased cancer risk within this gene desert. Previous work shows that one of these SNPs, rs6983267, plays an important role in regulating c-MYC through a 335 kb chromatin loop. TCF4, a transcription factor involved in WNT signaling, binds more strongly to the risk-associated G allele than the T allele. The rs6983267(G) allele has no effect on looping efficiency, but its stronger affinity for TCF4 increases the expression of c-MYC two-fold. The area surrounding rs6983267 is highly conserved and contains chromatin modifications that are characteristic of enhancers. Overall, this data supports the model that rs6983267 is located within a distal enhancer and regulates c-MYC expression through a large chromatin loop.

In one of my projects, we are using CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) to delete various sections of the rs6983267 enhancer in DLD-1 cells, a human colorectal cancer cell line. CRISPRs are RNA-directed nucleases that can be designed to make a double-stranded break in a specific DNA sequence. After making multiple size deletions in the enhancer, we will use RT-PCR to look at allele-specific c-MYC expression. DLD-1 cells are also heterozygous at rs4645953, a SNP in intron one of c-MYC. The C allele of the c-MYC SNP is linked to the G allele of rs6983267 (in the enhancer); therefore, we can use primers flanking the c-MYC SNP to determine allelic expression ratios. In addition, we will use chromatin conformation capture (3C) to study the loop between the rs6983267 enhancer and the c-MYC promoter. 3C allows us to detect the presence or absence of a chromatin loop. These tools will help us to determine which sequences within the rs6983267 enhancer are necessary for enhancer function and/or looping.

Email: elizabeth.a.sergison.gr@dartmouth.edu