The short-sequence design of DNA and its involvement in the 3-D structure of the genome

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 low-heterogeneity, GC-poor isochores are characterized by the presence of ol...

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Bibliographic Details
Published in:Scientific reports 2018-12, Vol.8 (1), p.17820-8, Article 17820
Main Authors: Lamolle, Guillermo, Sabbia, Victor, Musto, Héctor, Bernardi, Giorgio
Format: Article
Language:English
Subjects:
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Chromatin
Chromosome 21
Chromosomes
Chromosomes, Human, Pair 21 - chemistry
Deoxyribonucleic acid
DNA
Genome, Human
Genomes
Heterogeneity
Humanities and Social Sciences
Humans
Isochores
Isochores - chemical synthesis
Isochores - chemistry
multidisciplinary
Nucleosomes - chemistry
Nucleotide sequence
Nucleotides
Science
Science (multidisciplinary)
Topology
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Summary: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 low-heterogeneity, GC-poor isochores are 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 the lamina. In contrast, the high-heterogeneity GC-rich isochores are in the form of compositional peaks and valleys characterized by increasing gradients of oligo-Guanines in the peaks and oligo-Adenines in the valleys 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 100 Kb segments of chromosome 21, as well as those of the di- to octa-Adenines and di- to octa-Guanines in some representative 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 has strong implications for the biological role of non-coding sequences.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-35864-9