DNA folding influences gene activation

Washington: Scientists have made a medical breakthrough which may help bring new insights on how genes are activated.

Roughly 3 metres of DNA is tightly folded into the nucleus of every cell in our body. This folding allows some genes to be `expressed`, or activated, while excluding others.

Dr Tim Mercer and Professor John Mattick from Sydney`s Garvan Institute of Medical Research and Professor John Stamatoyannopoulos from Seattle`s University of Washington analysed the genome`s 3D structure, at high resolution.

Genes are made up of `exons` and `introns` - the former being the sequences that code for protein and are expressed, and the latter being stretches of noncoding DNA in-between.

As the genes are copied, or `transcribed`, from DNA into RNA, the intron sequences are cut or `spliced` out and the remaining exons are strung together to form a sequence that encodes a protein. Depending on which exons are strung together, the same gene can generate different proteins.

Using vast amounts of data from the ENCODE project, Dr Tim Mercer and colleagues have inferred the folding of the genome, finding that even within a gene, selected exons are easily exposed.

Mercer said that imagine a long and immensely convoluted grape vine, its twisted branches presenting some grapes to be plucked easily, while concealing others beyond reach.

He said that at the same time imagine a lazy fruit picker only picking the grapes within easy reach, asserting the same principle applies in the genome. Specific genes and even specific exons, are placed within easy reach by folding.

Mercer asserted that their study has provides the first indication that the three-dimensional structure of the genome can influence the splicing of genes.

He added that they can infer that the genome is folded in such a way that the promoter region - the sequence that initiates transcription of a gene - is located alongside exons, and they are all presented to transcription machinery.

Their findings have been published online in Nature Genetics.