DNA twists to control function

The three-dimensional structure of DNA affects gene expression.

A protein's function cannot be inferred from the linear sequence of its constituent amino acids. Its pattern of folding provides the function. Much the same is true of DNA, according to a study published today in Nature Genetics.

The serpentine convolutions of DNA expose certain exons and hide others, affecting their transcription, the study stated. Researchers imaged the genome's 3D structure at high resolution and compared it with known patterns of gene expression and splicing.

This means that digital models of DNA's functions are incomplete. The non-digital folding patterns of the genome control gene expression.

The study was led by Tim Mercer and Professor John Mattick from the Garvan Institute of Medical Research in Sydney, Australia, and John Stamatoyannopoulos from the University of Washington in Seattle.

"We 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," Mercer said in a Garvan Institute press release.

Mercer presented an image of DNA folded in a pattern that regulated expression by presenting or hiding regions, without chemically modifying them.

"Imagine a long and immensely convoluted grape vine, its twisted branches presenting some grapes to be plucked easily, while concealing others beyond reach," Mercer said in the press release. "At the same time, imagine a lazy fruit picker only picking the grapes within easy reach. The same principle applies in the genome. Specific genes and even specific exons, are placed within easy reach by folding."

The paper concluded that the 3D structure of DNA folding can generate complex patterns of interactions that explain some of the human genome's hitherto unexplained actions.

"The privileged demarcation of exons could readily generate transcriptional complexity from the modular architecture of the human genome, whereby a single exon can be spliced into a range of overlapping coding and noncoding transcripts," the paper stated.

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DNA twists to control function