The three-dimensional structure of the genome determines how genes are expressed, new research from the Garvan Institute of Medical Research and the University of Washington has found.

For the new research, the genome’s 3D structure was analyzed in detail and at high resolution, which yielded new insight into how/why some genes are expressed and others aren’t. Some background — there’s somewhere around three meters worth of DNA tightly folded within the nucleus of every one of the human body’s cells. Depending on the ‘folding’, some genes are ‘expressed’, while others aren’t.

The Garvan Institute of Medical Research continues:

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.

With the aid of the enormous amounts of data gathered by the ENCODE project, the researchers have now “inferred the folding of the genome, finding that even within a gene, selected exons are easily exposed.”

“Imagine a long and immensely convoluted grape vine, its twisted branches presenting some grapes to be plucked easily, while concealing others beyond reach,” explained Dr Tim Mercer, from the Garvan Institute of Medical Research in Sydney. “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.”

“Over the last few years, we’ve been starting to appreciate just how the folding of the genome helps determine how it’s expressed and regulated.”

“This study provides the first indication that the three-dimensional structure of the genome can influence the splicing of genes.”

“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.”

“This supports a new way of looking at things, one that the genome is folded around transcription machinery, rather than the other way around. Those genes that come in contact with the transcription machinery get transcribed, while those parts which loop away are ignored.”

The new findings were published in the journal Nature Genetics.

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