CORDIS
EU research results

CORDIS

English EN
Visualising how proteins fold DNA into topologically associating domains in single human cells

Visualising how proteins fold DNA into topologically associating domains in single human cells

Objective

How can phenotypic variations emerge from cells that carry the same genetic information? It is one of today’s great challenges to understand how genetic information is modulated inside the cell. Over the last decade, insight from genome-wide proximity-based ligation approaches revealed that the genome is organised in a hierarchical manner with the help of structuring proteins, and that this spatial organisation regulates the core functions of the genome, such as transcription, replication and repair. In this context, topologically associating domains (TADs) were identified as fundamental and functional building blocks of chromatin organisation above the nucleosome level. Despite its vital importance, our current understanding of the spatial organisation of TADs remains largely enigmatic. With the advent of super-resolution microscopy, tools are now available for studying genomic structures and their functional dynamics in situ at a resolution of 10 nm which corresponds to the size of a few nucleosomes.
The goal of this project is to reveal the principles of TAD organisation in human cells. To achieve this, I will employ a multidisciplinary imaging-based approach. I will simultaneously visualise the DNA backbone of TADs and architectural proteins involved in TAD structure applying 3D super-resolution microscopy. I will focus on the key TAD organisers CTCF and Cohesin, as well as on Mediator and Condensin II. Additionally, I will directly study their individual structuring function for TADs by their acute depletion. Integrating these data with quantitative measurements of absolute protein copy numbers, I will derive a data-driven model of inner TAD organisation in cells. These studies will provide the first 3D description of this fundamental chromatin super-structure and will further our understanding of genome architecture which is a prerequisite for understanding genome function.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Address

Meyerhofstrasse 1
69117 Heidelberg

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 174 806,40

Project information

Grant agreement ID: 842542

Status

Grant agreement signed

  • Start date

    1 July 2020

  • End date

    30 June 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 174 806,40

  • EU contribution

    € 174 806,40

Coordinated by:

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Germany