The elusive enzyme, whose presence in cells was suspected but not proven for decades, came to light in the laboratory of Yang Shi, HMS professor of pathology, and is described in a study published in the Dec. 16 online edition of Cell and appearing in the Dec. 29 print edition.

"This discovery will have a huge impact on the field of gene regulation," said Fred Winston, an HMS professor of genetics who was not involved with the work. "Shi and his colleagues discovered something that many people didn't believe existed."

The enzyme, a histone demethylase, removes methyl groups appended to histone proteins that bind DNA and help regulate gene activity. "Previously, people thought that histone methylation was stable and irreversible," said Shi. "The fact that we've identified a demethylase suggests a more dynamic process of gene regulation via methylation of histones. The idea of yin and yang is universal in biology; our results show that histone methylation is no different."

In the cell, yarnlike strands of DNA wrap around protein scaffolds built of histones. The histones organize DNA into a packed structure that can fit into the nucleus, and the packing determines whether the genes are available to be read or not. Acetyl, methyl, or other chemical tags appended to the histones determine how the histones and DNA interact to form a chromatin structure that either promotes gene activity or represses it.

Some histone tags, particularly acetyl groups, are known to be easily added and removed, helping genes to flick on and off when needed. But the addition of methyl groups was considered a one-way process that could only be
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Contact: John Lacey
public_affairs@hms.harvard.edu
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Harvard Medical School
16-Dec-2004