Until recently, proteins called "histones" have been the Rodney Dangerfields ("I don't get no respect!") of the biochemical world. Histones bind to DNA and wrap the genetic material into "beads on a string" in which DNA (the string) is wrapped around small blobs of histones (the beads) at regular intervals. In the past, many researchers believed that histones played a passive role in chromosome architecture and little role in specifically switching genes on and off. Now, scientists who remained true to histone research are basking in the glow of renewed respect for the dynamic role that these proteins are being found to play in the inheritance of specialized chromosome structures and the control of gene activity. Moreover, evidence suggests that defects in the establishment of proper chromosome structure by histones may activate or silence genes aberrantly and thus lead to disease.

In the August 10 issue of Science, Cold Spring Harbor Laboratory researcher Shiv Grewal and his colleagues report that seemingly small differences between two varieties of histone have dramatic effects on chromosome structure and gene expression. They found that "silent" regions of chromosomeswhere genes are kept "off" and DNA resists genetic recombinationcontain one variety of histone H3. In contrast, the researchers found that "active" regions of chromosomeswhere genes can be easily switched "on" and DNA can readily recombinecontain a slightly different variety of histone H3. Histone H3 in silent DNA had a "methyl" group attached to a particular lysine amino acid, #9. Histone H3 in active DNA had a methyl group attached to a different, nearby lysine amino acid, #4. (color illustration available)

Interestingly, Grewal and his colleagues showed that deleting "boundary elements" which mark the transition between silent and active regions of DNA allowed the spreading of lysine 9-methylated histones into neighboring DNA normally occupied by lysine 4-methylated hi
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Contact: Peter W. Sherwood, Ph.D.
sherwood@cshl.org
516-367-6947
Cold Spring Harbor Laboratory
9-Aug-2001

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