Disruption of one protein could lead to cancer
A Carolina lab was the first to identify a key process in animals that, when mutated, causes cells to multiply out of control.
Genes make up the blueprints and outline the process of building every living organism.
To ensure that the right genes are activated in the right cells, and in the right amounts at the right time, genes are constantly being regulated by small molecular machines made of proteins. When gene regulation fails, or specific genes are altered through mutation, the body is more predisposed to diseases such as cancer, Alzheimer’s and autoimmune disorders.
Now, for the first time in animals, the lab of Daniel McKay, associate professor of biology in the UNC College of Arts and Sciences and of genetics at the UNC School of Medicine, has identified a crucial focal point in the regulatory processes that govern cell identity.
Researchers discovered that a chemical alteration on a single protein, histone H3, is essential for controlling the genes that help cells remember their own identity and function. When the genes and proteins in charge of keeping these regulatory processes in check are mutated, cells will proliferate out of control or resist cell death pathways, two key features of cancer.
Cyril Anyetei-Anum, a doctoral candidate in the curriculum in genetics and molecular biology and member of the McKay lab, was lead author on the study, published in November in Genes and Development.
Our genomes are huge. Each cell contains over 6 billion DNA letters, that, if stretched out end-to-end, would measure 2 meters long. Small proteins called histones are tasked with tightly packaging all that DNA into every cell, like a librarian shoving books into a full bookcase. Histones also play key roles in gene regulation.
Small chemical modifications can be added to histones, which allow proteins to access the tightly bound DNA from their histone bookcases to turn “on” and “off” genes in the organism. With ready access to DNA information, the body can carry out gene expression or convert genetic information into protein products that carry out actions specified in the DNA code.
Scientists have long studied the processes that underlie gene expression and the chemical modifications of histones because of the downstream effects they have on cellular processes.
Over the past 10 years, the McKay lab has been collaborating with several labs at UNC-Chapel Hill to create an experimental animal model system they could use to study the role of histone proteins in regulating genes.
For this study, researchers used the fruit fly because of its simple genetics and the fact that its genetic elements are incredibly like that of humans. With the fruit fly model, McKay and colleagues first determined what was required to activate “master regulator” genes.
These genes are critical in the large-scale regulation of the early human body, including those that develop tissue and organ systems, produce specialized cells from stem cells, and aid cells in remembering their own identity and function.
If these genes are expressed at the wrong time or place, they can transform cells from one identity into another, which is one of the key features of diseases like cancer.
