Problems With Nuclear Membrane Could Play Part in Heart Disease, Leukemia, and Progeria

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Researchers at Salk University have completed a study that’s revealed how the nucleus acts on its contents in order to influence gene expression. They discovered that nuclear core components regulate the expression of cell identity genes through the interaction with super-enhancers. Salk Professor, Martin Hetzer, comments “Our research shows that, far from being a passive enclosure as many biologists have thought, the nuclear membrane is an active regulatory structure.”


The team discovered two particular proteins are actively associated with the parts of DNA known to trigger the expression of genes. By better understanding the way in which these proteins function, scientists gain a better insight into diseases that are linked to dysfunctional nuclear membrane components including heart disease, leukemia and some aging disorders such as progeria. The first author of the paper and a Salk staff scientist, Arkaitz Ibarra said, “Discovering that key regulatory regions of the genome are positioned at nuclear pores was very unexpected.”

Salk scientists discover that nuclear pore components regulate the expression of cell identity genes through functional interactions with super-enhancers. In the image, a super-enhancer driven cell identity gene (red dot) localizes in close proximity to the nuclear envelope (green) in the nucleus of human primary lung fibroblasts (blue). Click here for a high-resolution image Credit: Salk Institute
Salk scientists discover that nuclear pore components regulate the expression of cell identity genes through functional interactions with super-enhancers. In the image, a super-enhancer driven cell identity gene (red dot) localizes in close proximity to the nuclear envelope (green) in the nucleus of human primary lung fibroblasts (blue).
Click here for a high-resolution image
Credit: Salk Institute

Next, the team studied a human bone cancer cell line to see which areas of DNA interacted with nucleoporins. They pinpointed where two nucleoporins (Nup153 and Nup93) came in contact with the genome and looked into which genes were being affected and how. It was found that Nup153 and Nup93 both interacted with super-enhancers that are vital in determining cell identity and driving gene expression. Hetzer says, “People have thought the nuclear membrane is just a protective barrier, which is maybe the reason why it evolved in the first place. And it’s such an important area because so far, every membrane protein that has been studied and found to be mutated or mislocalized seems to cause a human disease.”



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