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Epigenetics and the Heart: Lysine Methyltransferase SETD7 Methylates Two Novel Residues on Histone H3

Semester: Summer 2023

Presentation description

Heart disease ends the lives of nearly 700,000 people each year and has been the leading cause of death in the United States since 1950. Around this time researchers discovered that some modifications around our genetic code could be changed to affect gene expression but leaves the DNA intact, which was later termed epigenetics. Today we’ve discovered that these epigenetic modifications, often post translational modifications (PTMS), regulate genes linked to cardiovascular disease. We focused our research on histone lysine methyltransferase SETD7, which is known to monomethylate histone H3K4. First, we conducted a literature search on SETD7 in the diseased heart and found that this methyltransferase is upregulated in multiple types of heart disease in both human and mice. Meanwhile, Setd7 is essential for cardiomyocyte differentiation in embryonic development. Previously SETD7 was known to methylate only 9 histone residues, none of which explain its effect in the heart. To investigate further, we researched its enzymatic activity and hypothesized that it modifies additional histone sites than have previously been identified. By means of western blotting and mass spectrometry, we determined that SETD7 monomethylated two novel residues on histone H3: lysine 36 (K36) and lysine 122 (K122). Although our understanding of both these residues is limited, we do know that K36 methylation is linked to DNA replication and genomic stability while K122 methylation has been downregulated in drug-resistant MCF-7/ADR cancer cells. More research is necessary for a complete understanding of SETD7 in the heart and all 11 lysine methylation sites. These epigenetic modifications may shine light on how these diseases develop, and how to better treat patients. The two novel methylation sites suggest that this lysine methyltransferase plays a more complex role than solely monomethylating histone H3K4. Further studies are necessary to discover the impact of these methylation sites.

Presenter Name: Braxton Bird
Presentation Type: Poster
Presentation Format: In Person
Presentation #58
College: Medicine
School / Department: Internal Medicine
Research Mentor: Sarah Franklin
Date | Time: Thursday, Aug 3rd | 10:30 AM