Nutrient regulated gene expression

CHIARA MURGIA: The human body is made of trillions of different cells, and each of them contain exactly the same DNA molecule and the same genetic information in the nucleus. That’s quite interesting concept, as cells can look very differently, and they actually can do very different jobs. Lymphocyte– it is very different from a hepatocyte or neuron cells, but they do contain and they are led by the same genetic information. What does it make those cells different from each other, starting from the same direction contained in their DNA? And what it is is the subset of genes that each of them express. So they have all the same genes, but only a portion of the genome is expressed.

Which set of genes each cell needs to express is regulated by a large number of different factors during development of an organism. Position factors create a really important role. Hormonal factor, growth factors, the vicinity of other genes, and of course, an important player is the environment. And in the environment, the diet almost always has an important role. We have been studying the ability of nutrients and food components to regulate gene expression since the late 80s, so this is not a new thing. And we have accumulated over the year a lot of information. For example, vitamin D or other aqua-soluble vitamins can freely get inside cells through biological membranes because they are actually soluble in lipids.

So it can go straight into the cytoplasm, where it binds a specific cellular receptor– a vitamin D receptor, that it goes into the nucleus and activate the expression of calcium transporter. And that’s one of the mechanisms how vitamin D effect calcium absorption in the intestine. Also, iron regulates the expression of genes that are involved in its metabolism directly, and that’s at post transcriptional level. So iron through the binding with an regulative iron-binding protein is able to regulate the stability of a messenger and the efficiency of translation. So we’re able now to investigate the effect on global scale of a given stimuli, such vitamin D action through its receptor.

So while we used to test one or few genes at a time, now we are in the position of test the effect, for example, of vitamin D on the expression of the global– what we call now transcriptive– all the genes at the same time. And that allowed to understand that the effect of vitamin D is also in other tissues that were not classically known as affected by the availability of these vitamins. For example, a nice experimental was done in skin, and we now know that through vitamin D receptor vitamin D affect and modulate the expression of a large number of genes.

And interestingly, the pathway, they were identified as modulated by vitamin D in its receptor are involved in cell proliferation and differentiation. And then can suggest that vitamin D availability can have an effect on the development of cancer– of skin cancer, for example. So the effort to complete the Human Genome Project was a big incentive to develop a really efficient new technology to sequence DNA and to analyse big, complex amount of data with new developed bioinformatics technique. On the one side, this is very exciting because we are uncovering mechanisms of interaction that we had no idea before, but also highlight how complex is the system.

So nutrients and food components are able to affect the physiology of cells in a way that we had no idea before.