( DNA wrapped around a core like ribbon ...)Scientists map key landmarks in human genome

Nucleosomes have multiple functions, including allowing several feet of DNA to be packed tightly into a cell's nucleus. They also regulate gene expression, or activity, by determining whether DNA sequences can be accessed by transcription factors, allowing the factors to regulate expression of a nearby gene.

It has long been assumed that these factors can't bind to a stretch of DNA that is bound by a nucleosome; they can, however, attach to DNA "linkers" between two nucleosomes. With their new method, Fisher's group found that transcription factor binding indeed typically occurs in the "linker" regions in between nucleosomes, rather than in the DNA regions that are tied up by the nucleosome complexes. These results suggest that nucleosome positioning controls the turning on or off of genes, and the nucleosomes can be relocated if cellular needs change.

Fisher, who heads Dana-Farber's Melanoma Program and is a professor of pediatrics at Harvard Medical School, conducts basic research on gene mutations involved in the deadly skin cancer. He said the work that led to the current paper began when his lab was studying the protein, MITF, made by one of these genes, which influences the expression of other genes.

"We wanted to understand how MITF regulates target genes, and specifically where in promoter regions of those genes does MITF bind," Fisher said. "In the process of this work, we asked whether MITF is binding between nucleosomes or on top of nucleosomes, and that led us to devise a method to ask where the nucleosomes are located."

The researchers used gene microarrays to which DNA associated with single nucleosomes was added. The nucleosomal DNA was derived from several cancer cell lines including melanoma and breast cancer, as well as sever
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Source:Dana-Farber Cancer Institute