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RNA Play a Vital Role in Gene Activity

fferent chromosome," said Chang. "This opens up the whole genome to potential regulation by ncRNAs." The research will be published in the June 29 issue of the journal Cell.

The researchers were investigating how human skin cells, or fibroblasts, know where they are in the body. They had previously shown in different types of cells that groups of genes known as HOX act as a sort of global positioning system by maintaining unique patterns of expression over many generations of cell division.

But until Rinn used a new type of gene chip called a tiling array in the new study to home in on nearby regions of DNA, they didn't know how the HOX expression patterns themselves were determined.

"I like to think of it as genomic scuba diving," said Rinn of the new experiments. The tiling array allowed him to map the boundaries of the regions around four clustered sets, or loci, of HOX genes, known as HOXA through HOXD, to near-nucleotide resolution. That's somewhat like zooming in on a single home from a satellite map on Google Earth. "It gives us an up-close, unbiased view of what's actually happening at the chromosomal level," said Rinn.

Not only did Rinn locate many previously unknown ncRNA genes nestled among the HOX genes, he also identified areas that serve as shared landing pads for proteins that either activate or suppress the neighboring regions. "It's a striking pattern," said Rinn. "Like a light switch, the same stretch of DNA can be used to turn genes either on or off, depending on their protein partners." But then Rinn looked more deeply.

The fact that the ncRNAs have remained virtually unchanged over millions of years suggests they may be playing non-traditional but vital roles in gene expression.

The researchers found that depleting one ncRNA dubbed HOTAIR, in the HOXC region on chromosome 12 of a skin cell, significantly increased the expression of HOXD genes on chromosome 2. Th
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