InsideChromatin SIGNED

Project "InsideChromatin" data sheet

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 Partnership

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 Project objective

Reading the genome is one thing – finding out how it functions, is something else altogether. The next big challenge to understand gene behaviour is deciphering (a) how the genome is organized in space and (b) how this organization influences its function. Inside Eukaryotic cells, genomic DNA is packed together with proteins into a remarkable structure known as chromatin. Nucleosomes, the building blocks of chromatin, interact with each other to enable high-density packaging. Our understanding of chromatin structure is limited by the lack of ‘close up views’ and molecular-level mechanistic information of how nucleosome interactions are regulated in vivo by many highly coupled factors.

InsideChromatin aims to develop a groundbreaking multiscale approach that will push the current limits of realistic computational modelling of in vivo chromatin structure. The vision is to achieve the first multiscale simulation study that describes nucleosome organization inside functionally different kilobase-scale domains, while explicitly accounting for the combination of epigenetic marks, the binding of architectural proteins, and nucleosome remodelling activity that distinguishes each domain. InsideChromatin will integrate atomistic simulations with two levels of coarse-graining and experimental data for validation to understand how nucleosome organization at kilobase scales leads to physical properties at megabase scales. The output from InsideChromatin will bring us closer to the ‘holy grail’ of deciphering the connection between genome characteristics, structure, and function.