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It's all about the packaging

07 Aug 2000

How our genetic information is encoded in the DNA double helix - the genetic code - is general knowledge. However, the fact that there are other coordinating elements is relatively new and still a hypothesis.

DNA is not a naked molecule, but twisted in many places and closely associated with proteins known as histones. DNA and histones together produce a structure that is known as chromatin because it could be stained in early experiments and visualised under the microscope. 

Histones used to be regarded as mere structural elements, a form of packaging that ensures that DNA is condensed to survive the processes of cell division undamaged. For some time now, it has been clear that histone proteins are very dynamic components of a sophisticated machinery that controls how genetic information is "read". 

Certain enzymes can modify histones by adding small molecule groups, thereby influencing their three dimensional structure. Scientists have now suggested that these minimal changes have defined functions, that they are coding elements in their own right: the hypothesis of the histone code was born.

Researchers at the IMP can now provide evidence that the histone code actually exists. This week, they present their work in the journal Nature. Thomas Jenuwein and his team identified an enzyme (methyltransferase) that has homologs in humans, mice and yeast. As Stephen Rea, a PhD student in the Jenuwein lab, was able to show, the enzyme attaches a methyl group to a specific site of a histone and thereby initiates further changes that lead to DNA condensation.

Strongly condensed DNA sections are particularly well packaged and thus very stable. However, this also means that the hereditary information cannot be read. In extreme cases, entire chromosomes are shut down forever, such as the inactive X chromosome in females. 

Less densely packed sections are more accessible, their information retrievable. However, they are also more unstable and might easily be damaged if the various forces acting during cell division were to have an effect on them. This is exactly what Dónal O'Carroll, another doctoral student, was able to show in his experiments. After division, cells in which genes for the histone-modifying enzyme were defective showed typical changes in the nucleus caused by disturbed division processes. Similar changes can also trigger tumour formation.

These recent results suggest that the elucidation of the histone code will be far more than the confirmation of a hypothesis. Complete decoding, according to the authors, will have far-reaching consequences for both biology and medicine.

Original Publication

Stephen Rea, Frank Eisenhaber, Dónal O'Carroll, Brian D. Strahl, Zu-Wen Sun, Manfred Schmid, Susanne Opravil, Karl Mechtler, Chris P. Ponting, C. David Allis & Thomas Jenuwein. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593–599, 10 August 2000.