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DNA microarrays used to investigate how proteins bind DNA
By Bijal P. Trivedi

Researchers are using DNA microarrays to investigate how proteins called transcription factors selectively bind to specific sequences of DNA.

A transcription factor regulates the activity of a gene by binding to a specific location in the gene's regulatory region. Understanding why proteins prefer particular DNA sequences will aid researchers in identifying which proteins activate or inhibit a specific gene.

Martha Bulyk, of Harvard Medical School in Boston, Massachusetts, and colleagues tested Zif268, a mouse transcription factor, to study its interactions with DNA. The Zif268 protein contains zinc-fingers—structures common to transcription factors—that directly interact with the DNA helix. Bulyk's team constructed a microarray with a range of unique DNA-binding sites. They also created a library of Zif268 mutants in which one of the three zinc fingers had been altered. Using the microarrays the researchers examined the DNA-binding preferences of each Zif268 mutant.

"This technology will also be immediately useful in engineering designer zinc-finger DNA-binding domains for the control of gene expression in biotechnology applications ranging from functional genomics to gene therapy," write the authors in the current issue of Proceedings of the National Academy of Sciences.

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Bulyk, M.L. et al. Exploring the DNA-binding specificities of zinc fingers with DNA microarrays. Proc Natl Acad Sci USA 98, 7158-7163 (June 19, 2001).

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