PT  - JOURNAL ARTICLE
AU  - Giorgio Bernardi
TI  - Chromatin domain formation: a new model
AID  - 10.1101/096487
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 096487
4099  - http://biorxiv.org/content/early/2017/05/10/096487.short
4100  - http://biorxiv.org/content/early/2017/05/10/096487.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 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 local wider nucleosome spacing associated with the high frequency of 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 (and increasing nuclease accessibility) due to decreasing nucleosome density and decreasing supercoiling. In conclusion, chromatin architecture appears not only to be encoded but also to be molded by isochores, the DNA units of genome organization. This “isochore molding” model of chromatin domains (both LADs and TADs) is essentially based on the differential binding of nucleosomes by isochore sequences and on the role of architectural proteins in closing TAD loops and ensuring TAD insulation.