Accepted_test

Disruption of inter-nucleosomal interactions leads to notable changes in genome architecture
by Ulianov S.V. | Khrameeva E.E. | Mikhaleva E.A. | Razin S.V. | Shevelyov Y.Y. | Institute of Gene Biology RAS | Skolkovo Institute of Science and Technology | NRC "Kurchatov Institute" | Institute of Gene Biology RAS | NRC "Kurchatov Institute"
Abstract ID: 51
Event: BGRS-abstracts
Sections: [Sym 1] Section “Fundamental and applied 3D genomics”

In the non-acetylated chromatin, the interaction of histone H4 tail of one nucleosome with the acidic patch interface formed by H2A/H2B dimer of another nucleosome leads to the aggregation of nucleosomes and to the compactization of chromatin fiber. At the same time, the acetylation of H4 tail prevents its binding with the acidic patch, thus disrupting inter-nucleosomal interactions and decondensing chromatin. Numerous chromatin proteins (such as viral peptide LANA or nucleoporin Elys) may also bind with the acidic patch. Since these proteins compete with the non-acetylated histone H4 tail for binding with the same interface, they may interfere with inter-nucleosomal interactions.

The goal of this study was to reveal changes in genome architecture occurring in response to artificially induced disturbance of inter-nucleosomal interactions. For this, we expressed in Drosophila S2 cells either LANA, or histone H2A lacking amino acids responsible for formation of acidic patch, and performed Hi-C analysis in these cells. We found that inhibition of binding of non-acetylated histone H4 terminus from one nucleosome with the acidic patch interface of another nucleosome upon expression of LANA or H2Amut leads to the loosening of spatial organization of topologically associating domains (TADs) consisting of inactive chromatin. At the same time, the expression of both protein factors leads to the increase in packaging density of TADs, consisting of active chromatin. The latter can be explained by inability of Elys/PBAP complex, known to decompact active chromatin, to bind with nucleosomes lacking acidic patch interface.