New Level of Order Discovered in DNA

A major new discovery about the structure of DNA molecules has been announced. Researchers have found there is a pattern to the organization of nucleosomes in DNA, which may explain why certain parts of the moleculare are accessible or inaccessible to transcription. This in turn may help explain how certain genes are conserved in nature, and why certain parts of the DNA molecule are more or less vulnerable to mutation and modification.

DNA – the long, thin molecule that carries our hereditary material – is
compressed around protein scaffolding in the cell nucleus into tiny
spheres called nucleosomes. The bead-like nucleosomes are strung along
the entire chromosome, which is itself folded and packaged to fit into
the nucleus. What determines how, when and where a nucleosome will be
positioned along the DNA sequence? Dr. Eran Segal and research student
Yair Field of the Computer Science and Applied Mathematics Department
at the Weizmann Institute of Science have succeeded, together with
colleagues from Northwestern University in Chicago, in cracking the
genetic code that sets the rules for where on the DNA strand the
nucleosomes will be situated. Their findings appeared today in Nature.

The benefits of this discovery could be numerous and far reaching…

The team’s findings provided insight into another mystery that has long
been puzzling molecular biologists: How do cells direct transcription
factors to their intended sites on the DNA, as opposed to the many
similar but functionally irrelevant sites along the genomic sequence?
The short binding sites themselves do not contain enough information
for the transcription factors to discern between them. The scientists
showed that basic information on the functional relevance of a binding
site is at least partially encoded in the nucleosome positioning code:
The intended sites are found in nucleosome-free segments, thereby
allowing them to be accessed by the various transcription factors. In
contrast, spurious binding sites with identical structures that could
potentially sidetrack transcription factors are conveniently situated
in segments that form nucleosomes, and are thus mostly inaccessible.

Since the proteins that form the core of the nucleosome are
among the most evolutionarily conserved in nature, the scientists
believe the genetic code they identified should also be conserved in
many organisms, including humans. Several diseases, such as cancer, are
typically accompanied or caused by mutations in the DNA and the way it
organizes into chromosomes. Such mutational processes may be influenced
by the relative accessibility of the DNA to various proteins and by the
organization of the DNA in the cell nucleus. Therefore, the scientists
believe that the nucleosome positioning code they discovered may aid
scientists in the future in understanding the mechanisms underlying
many diseases.