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Mice, men make livers differently

CAMBRIDGE, Mass. -- Scientists often study mice as a model for human biology and disease, because their basic biological processes are assumed to be essentially the same as those of humans.

But now, a team of MIT researchers has uncovered a surprising difference. In a study of gene regulation in mouse and human liver cells, they found that master regulatory proteins function in very different ways in mice and humans.

"Evolution has discovered several different ways to make a liver from the same building blocks," said Ernest Fraenkel, MIT assistant professor of biological engineering and leader of the research team. "Comparing these different ways of regulating genes may unlock some of nature's most closely guarded secrets."

The work, which will be published in the May 21 online edition of Nature Genetics, could help identify patterns in the extremely complicated control mechanisms involved in gene expression.

"You can think of it as two different dialects of the same language. By exploring the human and mouse versions, we hope to find an underlying grammar," said Fraenkel.

Every cell in the human (or mouse) body has the same collection of genes, but the genome of each cell is carefully regulated so that only certain genes are expressed. Regulatory proteins known as transcription factors control this expression by binding to specific locations within the genome and turning nearby genes on or off.

The researchers and their colleagues had previously worked out many aspects of gene regulation in the human liver, which is one reason the researchers chose to study the liver. In the current study they compared 4,000 human genes with nearly identical counterparts, known as homologous genes, from mouse liver cells.

Given the similarity between the two species DNA sequences, the researchers expected that transcription factors would bind to the same sites in most pairs of homologous genes. To their sur
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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
21-May-2007


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