PT - JOURNAL ARTICLE AU - Giorgio Bernardi TI - The Genomic Code: Isochores Encode and Mold Chromatin Domains AID - 10.1101/096487 DP - 2016 Jan 01 TA - bioRxiv PG - 096487 4099 - http://biorxiv.org/content/early/2016/12/23/096487.short 4100 - http://biorxiv.org/content/early/2016/12/23/096487.full AB - The mechanisms of formation of LADs, the lamina associated domains, and TADs, the topologically associating domains of chromatin, are not yet understood, even if several interesting models have been proposed so far. This problem was approached here by using as a starting point the observation that chromatin architecture has an isochore framework and by having a closer look at both the isochore structure and the isochore/chromatin domain connection. This approach showed that LADs essentially correspond to isochores from the very GC-poor, compositionally very homogeneous L1 family and from the “low-heterogeneity” L2 (or L2−) sub-family; LADs are compositionally flat, flexible chromatin structures that attach themselves to the nuclear lamina in self-interacting clusters. In contrast, TADs (neglecting those that coincide with LADs) comprise the increasingly GC-richer isochores from the “high-heterogeneity” L2 (or L2+) sub-family and from the H1, H2 and H3 families; these isochores were found to be in the form of single or (more frequently) multiple GC peaks that underlie individual chromatin loops or chromatin loop ensembles, respectively. TADs appear to be constrained into loops by the properties that accompany the increasing GC levels of isochore peaks, namely increasing bendability, increasing nuclease accessibility, decreasing supercoiling and decreasing nucleosome density. In conclusion, a “genomic code” underlies the encoding and shaping of chromatin architecture by the compositional features of isochores.