Dynamic recognition of the nucleosome core particle by select chromatin factors_HD_TU_SK_2024

Abstract 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 pairs. We report here computational evidence for an unusual emergence of asymmetry whereby the nucleosome binding affinities of the chromatin factors are altered by the DNA sequence on each side even though the protein factors bind chemically equivalent nucleosomal protein interfaces. Furthermore, none of these proteins interact directly with the nucleosomal DNA. Our atomistic molecular dynamics simulations suggest that the nucleosomal gyre that binds DNA strongly is also more preferred by most chromatin factors, including Sir3, PRC1, RCC1, and SAGA-DUB. However, a fifth chromatin factor, 53BP1, prefers the gyre with the weaker DNA binding high affinity. We suggest that this tunability in nucleosome affinity could be related to the function of the chromatin interactors as in the case of 53BP1 which could prefer loose DNA gyres for its DNA repair function.