Membranes not only protect the DNA inside cells but also regulate them, scientists at the La Jolla-based Salk Institute reported Thursday.
The research, published in the journal Genes & Development, found that a membrane — sort of a cellular container — acts on its contents to influence gene expression. The discovery 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,” said 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.”
Complexes of at least 30 different proteins, called nucleoporins, form pores in the membrane that control what goes in or out, the scientists said. The pore complexes, beyond being mere gateways into the nucleus, have surprising regulatory effects on the DNA inside, according to the researchers.
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. Experiments that silenced either protein resulted in abnormal gene expression from the regions.
“People have thought the nuclear membrane is just a protective barrier, which is maybe the reason why it evolved in the first place,” Hetzer said. “But there are many more regulatory levels that we don’t understand.”
He said it’s an important area to study because so far, every membrane protein that has been studied and found to be mutated or “mis-localized,” causes a human disease.
–City News Service