The folding of chromatin is an inherent property of the genome to incorporate the DNA in the cell nucleus. Recent advances using chromosome conformation capture technologies have shown that the genome is folded in structured domains, so-called TADs. Structural variations, as they often occur in human genetic disease, can interfere with TAD configuration and thus result in altered gene expression and consecutive disease. By re-engineering human aberrations in mice it was shown that TADs and their boundaries are an essential component when interpreting structural variations.
A mathematical analysis of human gene promoter sequences shows that these promoters fall into two distinct classes. A number of features correlate with these two classes, suggesting that this distinction is actually a reflection of different regulatory mechanisms. This article summarizes sequence features and biological properties specific for the promoters of the two classes. We explain how a mathematical analysis of whole-genome data could point towards particular biological mechanisms.