Now that we have piles and piles of widely available genome sequence, one of our main tasks as biologists is to figure out how to read what’s in there. Protein-coding sequences have long been relatively easy to read, ever since the genetic code was worked out. Non-coding regulatory sequences – enhancers and promoters – are much more difficult to interpret, obviously. Usually our first task is to identify the individual binding sites for gene-regulating proteins in these sequences. But then what? Well, most people stop there, happy to have identified the necessary parts of the gene regulating machinery, but many of us are interested in learning the underlying logic by which this machinery operates – we want to learn the grammar of regulatory DNA. The question is, how does a particular combination of regulatory binding sites give rise to a particular pattern of gene expression? In my biased opinion, this the real secret of life – how your cells read information in your DNA in order to turn on the right genes at the right place in the right time.
So, how do we read non-coding, regulatory DNA? One way that has proven very useful is take an approach from the 1920’s that was developed to understand the physics of magnets. No, I’m not talking about the pseudoscience of biomagents; I’m talking about Ising models. Continue reading “How DNA is like a Magnet”

