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Salk Institute for Biological Studies Release: Heart Disease, Leukemia Linked To Dysfunction In Nucleus



11/4/2016 6:45:35 AM

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LA JOLLA, Calif., Nov. 3, 2016 /PRNewswire-USNewswire/ -- We put things into a container to keep them organized and safe. In cells, the nucleus has a similar role: keeping DNA protected and intact within an enveloping membrane. But a new study by Salk Institute scientists reveals that this cellular container acts on its contents to influence gene expression, a discovery which could provide insight into diseases that appear to be related to dysfunctional nuclear membrane components, such as leukemia, heart disease and aging disorders.

"Our research shows that, far from being a passive enclosure as many biologists have thought, the nuclear membrane is an active regulatory structure," says Salk Professor Martin Hetzer. "Not only does it interact with portions of the genome to drive gene expression, but it can also contribute to disease processes when components are faulty." The work was published Genes & Development on November 2, 2016.

Complexes of at least thirty different proteins, called nucleoporins, form gateways (pores) in the membrane, controlling what goes in or out. But as the Hetzer lab's work on nucleoporins shows, these nuclear pore complexes (NPCs), beyond being mere gateways into the nucleus, have surprising regulatory effects on the DNA inside.

Hetzer, first author Arkaitz Ibarra and colleagues used a molecular biology technique to pinpoint where two nucleoporins, Nup153 and Nup93, came into contact with the genome. They discovered that Nup153 and Nup93 interacted with stretches of the genome called super-enhancers, which are known to help determine cell identity. Since every cell in our body has the same DNA, what makes a muscle cell different from a liver cell or a nerve cell is which particular genes are turned on, or expressed, within that cell. In the Salk study, the presence of Nup153 and Nup93 was found to regulate expression of super-enhancer driven genes and experiments that silenced either protein resulted in abnormal gene expression from these regions.

"People have thought the nuclear membrane is just a protective barrier, which is maybe the reason why it evolved in the first place. But there are many more regulatory levels that we don't understand. And it's such an important area because so far, every membrane protein that has been studied and found to be mutated or mis-localized, seems to cause a human disease," says Hetzer.

CONTACT: Salk Communications at press@salk.edu

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/heart-disease-leukemia-linked-to-dysfunction-in-nucleus-300357050.html

SOURCE Salk Institute


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