Eagen Kyle P, Hartl Tom A, Kornberg Roger D
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Departments of Developmental Biology, Genetics, and Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2015 Nov 5;163(4):934-46. doi: 10.1016/j.cell.2015.10.026.
Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes.
化学交联和DNA测序揭示了间期细胞核内染色体内部相互作用的区域，即拓扑相关结构域（TADs），这些区域散布着很少或没有相互作用的区域。我们发现TADs及其之间的区域与果蝇多线染色体的带和间带相对应。我们进一步证实了果蝇多线细胞和二倍体细胞之间TADs的保守性。通过对多线染色体光学显微镜照片的直接测量，我们进而推断出二倍体细胞核中染色质折叠的状态。两种折叠状态，即包含调控区域和启动子的完全伸展纤维，以及浓缩至10倍的包含活跃基因编码区域的纤维，构成了核内部的常染色质。浓缩至30倍的染色质纤维，包含非活跃基因的编码区域，代表了核周边的异染色质。因此，分子分析与直接观察的结合揭示了间期染色体的结构。
