Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

6-POS Board 6 EFFECTS OF CTCF AND COHESIN COMPLEXES ON CHROMATIN

ARCHITECTURE AND GENOME TOPOLOGY Aymen Attou 1 ; Gero Wedemann 1 ; Tilo Zülske 1 ; 1 Hochschule Stralsund, Stralsund, Germany

The sophisticated spatial organization of DNA in eucaryotes starts from nucleosome chains forming chromatin loops that can cluster together establishing fundamental units called topologically associating domains (TADs). TADs are an important factor for gene regulation by facilitation or repressing long range contacts in the genome. Those loops are formed and held together by a ring-shaped protein complex called cohesin together with the effect of CTCF, an 11-zinc finger DNA-binding protein. This cohesin complex causes a bi-directionally extruding process and forms a loop anchor when encountering the right directed CTCF. A loop has a residence time of several minutes. For the purpose of clarifying the spatial structure of a loop we investigated these processes at a super nucleosomal level, where we modeled the 3D-nuclear organization by computer simulations in the presence and depletion of cohesin and CTCF. The simulations are based on our established coarse grained model utilizing a Metropolis-Monte Carlo procedure combined with replica exchange to generate a statistical representative ensemble of configurations in thermal equilibrium. We studied differences in the spatial structure and of contacts probabilities of different domains, These results of systems with present and depleted cohesin and CTCF were compared with experimental data. It allowed us to understand the role of cohesin and CTCF and their impact on the 3D structure of chromatin.

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