Gene expression is affected not only by nucleotide sequence, but also by DNA folding


An artistic representation of the double helix. Source: Pixabay

Dutch researchers from Leiden University have found that how our DNA is folded is a programmed command present in our genes, and the command varies from life-form to life-form instead of following a generic standard.

While traditionally we may think that genetic information is only present in the way that the DNA molecules G-A-T-C are combined, prevalent research shows that the way in which the molecules are bound into coils expose the outer molecules of the coil to express themselves while leaving the inner molecules as latent in expression.

In this study, scientists tried to gauge if ‘how the coils were wrapped was a function of energy alone or could actually be a programmed positioning of the molecules, thereby preferring some molecules to form proteins over others. This possible preferential wrapping is termed as “mechanical information”.

The scientists tried to answer three questions:

  1. Do mechanical properties of the base-pair alone determine nucleosome positioning?
  2. Can nucleosomes be freely positioned on top of genes?
  3. Can classical genetic information and mechanical information provide combined effects?

Source: Pixabay, edited by Author

Using computational modelling, the researchers allowed molecular sequences freedom in exploring the sequence space to wrap themselves into a nucleosome. It was found that dinucleotides combinations of CC, CG, GC, GG peaked around positive roll positions (minor grooves facing outwards in a nucleosome) and AA, AT, TA, TT peaked around negative roll positions (minor grooves facing inwards in a nucleosome) for the most energetically favourable wrapping of DNA around histones. In particular, high-affinity (more tightly wrapped) nucleosomes showed GC at positive roll positions.

Nucleosomes were computationally found to position themselves in ways that the molecules faced least resistance from one-another to form DNA coils. These computationally found positions were typically very close to the positions of previously mapped nucleosomes.  Using this information, the scientists hypothesized that shifting the nucleosomes slightly to other energy minima points may be possible.

Further calculations proved that nucleosomes sometimes held less favourable energy minima points in forming the coil than would be computationally expected, hence there seemed to be a dual mechanism at work where genetic information was preferrentially positioned to allow one type of expression over another.

Thus, information in our genes are preserved, and expressed not only by the dinucleotide coding pairs (AA, CG etc.) but also by how the string folded into itself thereby exposing some molecules preferentially over others.

Such a study would then open up the possibility of modifying gene expression through mechanical manipulation of the string alone, rather than having to modify the dinucleotides found within the gene.

The paper was first published in PLOS on June 7, 2016 titled “Multiplexing Genetic and Nucleosome Positioning Codes: A Computational Approach” by Eslami-Mossallam et al.

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