Science Department, Roma Tre University, Viale Marconi 446, 00146, Rome, Italy.
Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Naples, Italy.
Bioessays. 2019 Dec;41(12):e1900106. doi: 10.1002/bies.201900106. Epub 2019 Nov 8.
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.
最近的研究揭示了 1）人类基因组的隔区可分为两个超家族，其特征是具有两种不同的长程 3D 结构，以及 2）这些结构主要基于短序列的分布和拓扑结构，塑造了初级染色质域（并定义核小体结合）。更具体地说，GC 含量低、基因含量低的隔区是低异质性序列，带有寡 A 刺，塑造了核纤层相关域（LAD），而 GC 含量高、基因含量高的隔区则具有单一或多个 GC 峰，塑造了拓扑关联域（TAD）。这些“初级 TAD”的形成可能在黏合蛋白和 CTCF 的作用下被挤出。最后，基因组密码负责对初级染色质域（LAD 和初级 TAD，即“基因空间”/“空间隔室”）进行普遍编码和塑造，解决了“非编码 DNA”、“垃圾 DNA”和“自私 DNA”的长期问题，从而为基因组的形成提供了一个新的视角。
