Biology subjects

Bernardi, G.

Publications and source records attributed to Bernardi, G..

21 records · Page 2Linked to original sources

bioRxiv2018

The short-sequence design of human chromosomes

Recent investigations have shown that isochores are characterized by a 3-D structure which is primarily responsible for the topology of chromatin domains. More precisely, an analysis of human chromosome 21 demonstrated that GC-poor isochores are low-heterogeneity sequences characterized by the presence of oligo-Adenines that are intrinsically stiff, curved and unfavorable for nucleosome binding. This leads to a structure of the corresponding chromatin domains, the Lamina Associated Domains, or LADs, which is well suited for interaction with lamina. In contrast, the high-heteorogeneity GC-rich isochores are in the form of compositional peaks characterized by gradients of oligo-Guanines that lead to increasing nucleosome depletions in the corresponding chromatin domains, the Topological Associating Domains, or TADs. These results encouraged us to investigate in detail the di- and tri-nucleotide profiles of 100Kb segments of chromosome 21, as well as those of the di- to octa-Adenines and di- to octa-Guanines in several regions of the chromosome. The results obtained show that the 3-D structures of isochores and chromatin domains depend not only upon oligo-Adenines and oligo-Guanines but also, to a lower but definite extent, upon the majority of di- and tri-nucleotides. This conclusion, which applies to all human chromosome, has strong implications for the biological role of non-coding sequences.

genomics↗

bioRxiv2018

The formation of chromatin domains: a new model

In spite of the recent advances in the field of chromatin architecture1,2, the formation mechanism of chromatin domains, TADs, the topologically associating domains, and LADs, the lamina associated domains, is still an open problem. While previous models only dealt with TADs and essentially relied on the architectural proteins CTCF and cohesin, the model presented here concerns both TADs and LADs and is primarily based on the corresponding DNA sequences, the GC-rich and GC-poor isochores, more specifically on their newly discovered 3-D structures. Indeed, the compositionally homogeneous GC-poor isochores were shown to be locally stiff because of the presence of interspersed oligo- Adenines4,5, whereas the compositionally heterogeneous GC-rich isochores were found to be peak-shaped and characterized by increasing gradients of GC and of interspersed oligo- Guanines. In LADs, oligo-Adenines induce local nucleosome depletions4,5 that are responsible for a wavy structure well adapted for interaction with the lamina. In TADs, the increasing GC levels and increasing oligo-Guanines of the isochore peaks are responsible for a decreasing nucleosome density5,6, a decreasing supercoiling7 and an increasing accessibility8. These factors mould the loops of \"primary TADs\", that lack self-interactions since they are CTCF/cohesin-free, yet transcriptionally functional structures9-11. This \"moulding step\" is followed by a second step, in which the cohesin rings bind to the tips of the \"primary TADs\" and slide down the loops. This process is very likely due to Scc2/Nipbl, an essential factor not only for loading cohesin, but also for stimulating its translocation12 and its ATPase activity13. This \"sliding step\" creates self-interactions in the loops and stops at the CTCF binding sites located at the base of the loops that are thus closed and insulated.

genomics↗

bioRxiv2016

THE GENOMIC CODE: ISOCHORES ENCODE AND MOLD CHROMATIN DOMAINS

The formation of mammalian chromatin domains was investigated by analyzing the domain/isochore connection. This showed that LADs correspond to GC-poor isochores and are compositionally flat, flexible chromatin structures because of the local nucleosome depletions associated with the presence of oligo-As. In contrast, TADs correspond to GC-rich isochores that consist of single or (much more frequently) multiple, GC peaks that shape the single or multiple, loops of TADs. Indeed, the increasing nucleosome depletions linked to the GC gradients of isochore peaks lead to an increasing chromatin flexibility (accompanied by an increasing accessibility and decreasing supercoiling). In conclusion, isochores not only encode but also mold chromatin architecture; while architectural proteins play a role in closing and insulating TAD loops. An extension of this model concerns the encoding of open and closed chromosome compartments by alternating GC-rich and GC-poor isochores, the interactions among compartments defining the 3-D chromosome folding.

genomics↗