Research Information System
2nd EuroHPC user day, EuroHPC 2024, Amsterdam, Netherlands, 22 - 23 October 2024, vol.255, pp.130-139, (Full Text)
The intricate interactions between the nucleosome core particle and chromatin-binding proteins control essential biological functions templated by DNA. The nucleosome is a symmetrical and disc-shaped nucleoprotein which binds several chromatin factors in a 2:1 stoichiometry. We report computational evidence for a DNA-sequence-driven emergence of asymmetry whereby the nucleosome binding affinities of the chromatin factors are altered on each side even though the protein factors bind chemically equivalent proteinous interfaces of the nucleosome. Furthermore, none of these proteins interact directly with the nucleosomal DNA. Using atomistic molecular dynamics simulations, we surveyed five chromatin factors that are known to bind the nucleosome in a 2:1 stoichiometry. In four factors, we found that the nucleosomal gyre that binds DNA strongly is also more preferred. These factors are Sir3, PRC1, RCC1, and SAGA-DUB. However, a fifth chromatin factor, 53BP1, prefers the gyre with the weaker DNA binding with higher affinity. We argue that this tunability in nucleosome affinity could be related to the function of the chromatin interactors as 53BP1 could prefer loose DNA gyres to execute its DNA repair function.