Prof. Grzegorz Wilczynski, Nencki Institute of Experimental Biology, Nuclear organisation of the genome: from structure to function

event date: 29 March 2019

The Centre of New Technologies invites to a seminar by

Prof. Grzegorz Wilczyński

Nencki Institute of Experimental Biology

Nuclear organisation of the genome: from structure to function

Date: March, 29th(Friday), 2019 at 12 p.m.

Venue: Centre of New Technologies, Banacha 2C,
Lecture Hall 0142 (Ground floor)

Host: Prof. Dariusz Plewczyński


Abstract: A principal component of the cell nucleus is chromatin, which is a complex of DNA encoding genetic information, and various proteins, the major ones being histones. The chromatin of interphase nuclei is a decondensed form of mitotic chromosomes. There was an one hundred years-long debate, about chromosome arrangement in interphase cells. In 1980s, it was proven that each decondensed chromosome occupies an integral territory within the cell nucleus. Recently, using a family of biochemical approaches, so-called chromosome conformation capture (3C) techniques, it was demonstrated that within a chromosome territory, smaller integral domains exist, namely, topologically-associated domains (TADs) or chromatin contact domains (CCDs). TADs/CCDs are supposed to be basic units of the higher-order chromatin folding. There are multiple spatial chromatin interactions inside these domains, but relatively low numbers of interactions of chromatin between the individual domains. The interactions are thought to have a physical form of loops of chromatin fibers. The loops could bring together genes and their regulatory regions, such as enhancers, into a close spatial proximity, despite the fact that they can be separated by hundreds of thousands base pairs in the linear DNA sequence. The existence of TADs/CCDs is well established by biochemical methods, however, their visualization by microscopy has not been, so far, done in detail. Thus, even basic physical features of these units, such as their diameters, are not known. We have created a new method, combining electron microscopy and in situ hybridization (3D-EM-ISH), to unravel the shape of TADs/CCDs with the resolution of a few nanometers. We have found that such structural units do exist, but their definition, based on biochemical techniques averaging millions of cells, is not always correct with regard to individual cells. For the first time, we defined precisely the diameters and shapes of TADs/CCDs. In combination with computer modeling, our morphological approach can provide a deeper knowledge of chromatin structure and function.