Team investigates chemical modifications to gain deeper insight into genetic regulation mechanisms


DNA, which has a double-helical structure, can have many mutations and genetic variants. Source: NIH

Scientists at the University of North Carolina at Chapel Hill have determined whether a specific chemical modification of a genome packaging protein, called a histone, affects gene activity and cell proliferation, according to the paper, “Drosophila melanogaster Set8 and L(3)mbt Execute Gene Expression Independently of Histone H4 Lysine 20 Methylation,” published in Genes and development.

In their research, the group found that removing the enzymes responsible for adding a specific chemical modification to a histone or the protein that binds it disrupts gene activity and cell proliferation. However, these disruptions are not directly caused by the chemical modification itself, which contradicts current models in the field.

“Our study has led to a better understanding of the mechanisms of genetic regulation,” said Bob Duronio, co-author and professor of biology. “This understanding provides fundamental information that could help us develop new treatments for diseases such as cancer that result from defects in the regulation of gene activity and cell proliferation by targeting Set8 pathways and mechanisms that are independent of histone modifications.”

Initially, the research group wanted to find out whether a chemical modification of a particular histone, added by an enzyme called Set8, was crucial for gene expression and cell growth, as previous studies in the field had predicted.

Contrary to earlier predictions, their studies showed that Set8 controls gene activity and cell proliferation through a mechanism other than chemical modification of the histone protein. Thus, a basic science study has improved our understanding of genetic regulation, which is important for understanding human diseases such as cancer.

Unlike previous studies, the researchers used a new genetic method developed through a collaborative effort at UNC-Chapel Hill to determine the function of histone modifications independently of enzymes such as Set8.

These research methods have the potential to reveal new functions of histone-modifying enzymes, shifting attention from the chemical modification of histones to broader roles of the enzyme, providing new insights into the mechanisms of gene regulation.

More information:
Aaron T. Crain et al., Drosophila melanogaster Set8 and L(3)mbt play roles in gene expression independent of histone H4 lysine 20 methylation, Genes and development (2024). DOI: 10.1101/gad.351698.124

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