法国蒙彼利埃大学Giacomo Cavalli、Frédéric Bantignies等研究人员合作发现，单细胞基因组可被组织进TAD和染色质纳米域中。该项研究成果于2020年10月19日在线发表在《自然—遗传学》杂志上。

Title: Regulation of single-cell genome organization into TADs and chromatin nanodomains

Author: Quentin Szabo, Axelle Donjon, Ivana Jerkovi, Giorgio L. Papadopoulos, Thierry Cheutin, Boyan Bonev, Elphge P. Nora, Benoit G. Bruneau, Frdric Bantignies, Giacomo Cavalli

Issue&Volume: 2020-10-19

Abstract: The genome folds into a hierarchy of three-dimensional structures within the nucleus. At the sub-megabase scale, chromosomes form topologically associating domains (TADs)1,2,3,4. However, how TADs fold in single cells is elusive. Here, we reveal TAD features inaccessible to cell population analysis by using super-resolution microscopy. TAD structures and physical insulation associated with their borders are variable between individual cells, yet chromatin intermingling is enriched within TADs compared to adjacent TADs in most cells. The spatial segregation of TADs is further exacerbated during cell differentiation. Favored interactions within TADs are regulated by cohesin and CTCF through distinct mechanisms: cohesin generates chromatin contacts and intermingling while CTCF prevents inter-TAD contacts. Furthermore, TADs are subdivided into discrete nanodomains, which persist in cells depleted of CTCF or cohesin, whereas disruption of nucleosome contacts alters their structural organization. Altogether, these results provide a physical basis for the folding of individual chromosomes at the nanoscale.

DOI: 10.1038/s41588-020-00716-8

Source: https://www.nature.com/articles/s41588-020-00716-8