The Genomic Code: A Pervasive Encoding/Molding of Chromatin Structures and a Solution of the “Non‐Coding DNA” Mystery

• Published in: BioEssays Vol. 41; no. 12; pp. e1900106 - n/a
• Main Author: Bernardi, Giorgio
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2019
• Subjects: Animals; Cell Cycle Proteins - metabolism; Chromatin; Chromatin - metabolism; chromatin folding principles; Chromosomal Proteins, Non-Histone - metabolism; Cohesin; Cohesins; Deoxyribonucleic acid; DNA; DNA - genetics; DNA - metabolism; Domains; Extrusion; Gene sequencing; Genome, Human - genetics; Genomes; Genomics - methods; Heterogeneity; Humans; Isochores; Isochores - metabolism; lamina‐associated domains; Molds; Nucleotide sequence; topologically associating domains; Topology; isochores; chromatin folding principles; lamina-associated domains; topologically associating domains
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201900106

Recent investigations have revealed 1) that the isochores of the human genome group into two super‐families characterized by two different long‐range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC‐poor, gene‐poor isochores are low‐heterogeneity sequences with oligo‐A spikes that mold the lamina‐associated domains (LADs), whereas GC‐rich, gene‐rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (TADs). The formation of these “primary TADs” may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the “gene spaces”/“spatial compartments”) resolves the longstanding problems of “non‐coding DNA,” “junk DNA,” and “selfish DNA” leading to a new vision of the genome as shaped by DNA sequences. GC‐poor isochores encode lamina‐associated domains that are folded (locally and/or globally) at the level of oligo‐A sequences (yellow boxes). GC‐rich isochores, characterized by GC gradients (yellow to red color), encode primary topologically associating domains (TADs) that are folded by GC‐blocks (black arrowheads) and may be extruded into TADs by cohesin and insulated by CTCF.