PT  - JOURNAL ARTICLE
AU  - Giorgio Bernardi
TI  - The formation of chromatin domains: a new model
AID  - 10.1101/096487
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 096487
4099  - http://biorxiv.org/content/early/2017/04/05/096487.short
4100  - http://biorxiv.org/content/early/2017/04/05/096487.full
AB  - The mechanisms of formation of LADs, the lamina associated domains, and TADs, the topologically associating domains of mammalian chromatin, were investigated here by using as a starting point the observation that chromatin architecture relies on an isochore framework and by doing a new analysis of both isochore structure and the isochore/chromatin domain connection. This approach showed that LADs correspond to isochores from the very GC-poor, compositionally very homogeneous L1 family and from the “low-heterogeneity” L2 (or L2−) sub-family; in fact, LADs are compositionally flat, flexible chromatin structures (because of the nucleosome depletion associated with the frequent oligo-A’s) that attach themselves to the nuclear lamina in self-interacting clusters. In contrast, TADs correspond to the increasingly GC-richer isochores from the “high-heterogeneity” L2 (or L2+) sub-family and from the H1, H2 and H3 families. These isochores, making the framework of the individual chromatin loops or of the chromatin loop ensembles of TADs, were found to consist of single or multiple GC peaks. The self-interacting single or multiple loops of TADs appear to be shaped by the property that accompany the increasing levels of GC and CpG islands in their isochore peak backbones, namely by an increasing bendability due to decreasing nucleosome density which is accompanied by decreasing supercoiling and increasing nuclease accessibility. In conclusion, chromatin architecture appears to be encoded and molded by isochores, the DNA units of genome organization. This “isochore encoding/molding model” of chromatin domains represents a paradigm shift compared to previously proposed models. Indeed, the latter only rely on the properties of architectural proteins, whereas the new model is essentially based on the physico-chemical properties of isochores and on their differential binding of nucleosomes.