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. and its role on the structure of the genome. This review deals exactly with this problem and shows, on the basis of past [4][5][6] and recent [7][8][9][10] published findings, that there is a fundamental link between DNA structure and chromatin structure, the "genomic code," which involves the encoding and molding of chromatin structure. Furthermore, being pervasive in the genome, the genomic code solves old outstanding problems, such as the "non-coding DNA," "junk DNA," or "selfish DNA."A good starting point for this introduction is to recall three early observations that are the roots of the recent findings because they concern DNA conformation and its link with the distribution of short sequences in the genome. This will be done not merely for historical reasons but because of their relevance to the recent results under review. Fifty five years ago, it was found [11] that calf thymus DNA undergoes a reversible decrease in viscosity in the sub-melting temperature range, indicating a reversible change in the configuration of ≈35% GCpoor DNA molecules. Five years later, two approaches, developed in order to fractionate DNAs on the basis of composition, provided information on their 3D conformation and their shortsequence frequencies. The background of the first approach was the chromatography of proteins on hydroxyapatite, a type of calcium phosphate, which had been shown to separate phosphoproteins according to their phosphate levels. [12] When applied to DNA, this approach separated native from denatured DNA, a "collapsed" structure that is eluted at a lower phosphate molarity because it has less phosphates available for binding to the calcium of hydroxyapatite. [13] In 1968, the discovery was made that hydroxyapatite could also separate yeast nuclear DNA (38% GC) from mitochondrial DNAs (18% GC in wild-type cells down to 4% GC in different "petite" mutants), the latter of which are eluted at increasingly higher phosphate molarities. This is because, being increasin...