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Movie Captures Genome in Action

By Nancy Touchette

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Movie shows how cell makes new protein (blue) from DNA code.
For the first time ever, researchers have captured on film how a gene goes about the business of directing a cell to make a protein.

Researchers at Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, tagged different molecules different colors so they could see the process by which a living cell makes protein from DNA within its nucleus. The process is much more dynamic than they had imagined.

Most studies of gene expression are conducted on isolated genes in the test tube and focus on only one step of the whole process. The Cold Spring Harbor team put it all together.

“We wanted to develop a system where we could study all aspects of the system,” says David L. Spector, who led the research. “We wanted to see gene expression played out in real time and space.”

The process of gene expression—making a protein from the DNA code—occurs in several steps. The gene sequence is first copied from the DNA strand into a similar but smaller molecule known as RNA. The RNA then travels out of the nucleus and its sequence is “read” by cell machinery that translates it into a specific protein.

Spector and his colleagues designed a gene sequence that could be inserted into the human genome. Once there, it could be turned on, or activated, at will and the ensuing sequence of events could be directly visualized by labeling DNA, RNA, and protein different colors in living cells.

The movie first shows a tightly compacted region of DNA opening up as the gene is activated. RNA—tagged yellow with a fluorescent protein—appears first in the nucleus and then moves out to the cytoplasm, the region of the cell surrounding the nucleus. Ultimately, blue-colored protein appears in the cytoplasm in structures called peroxisomes.

The researchers also labeled some of the proteins that package the DNA and were able to see that one of those proteins is replaced by a variant form that specifically zeroes in on the region of DNA that is being read.

Related Links
Gene Expression Movie
(AVI Format - 11.2 MB)
Spector Lab
Not all genes are active in a cell at a given time. Some genes in specialized cells are only turned on when needed and others are shut down permanently. Researchers studying stem cells and embryonic development are keenly interested in how the genome is programmed so that cells become the kind of cells needed by the body. And many diseases are thought to result from genes or combinations of genes being activated or silenced inappropriately.

Spector says his system can provide a direct view of gene expression and may help researchers understand what happens when things go wrong. He envisions inserting the easily visualized gene that he constructed into specific spots in the genome to get a clearer view of how genes are regulated in the context of a living cell.

“We might also use this system to see how small molecules such as anticancer drugs work in a living cell,” says Spector. “We could get a direct view into whether a drug is shutting down gene activation or affecting the way RNA is processed. Ultimately this could help us do a better job at identifying and designing new drugs.”

Janicki, S.M. et al. From silencing to gene expression: real-time analysis in single cells. Cell 116, 683-698 (March 5, 2004).

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