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Scientists discover a genetic code for organizing DNA within the nucleus

g the DNA sequence alone, were able to accurately predict a large number of nucleosome positions in yeast cells.

Segal and his colleagues accomplished this by examining around 200 different nucleosome sites on the DNA and asking whether their sequences have something in common. Mathematical analysis revealed similarities between the nucleosome-bound sequences and eventually uncovered a specific "code word." This "code word" consists of a periodic signal that appears every 10 bases on the sequence. The regular repetition of this signal helps the DNA segment to bend sharply into the spherical shape required to form a nucleosome. To identify this nucleosome positioning code, the research team used probabilistic models to characterize the sequences bound by nucleosomes, and they then developed a computer algorithm to predict the encoded organization of nucleosomes along an entire chromosome.

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 identifi
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Source:American Committee for the Weizmann Institute of Science


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