Strukturelle Umlagerungen des Histonoktamers verändern DNA Position
Zusammenfassung der Projektergebnisse
In this project we have solved many structures of nucleosomes in different conformations. Nucleosomes, the basic unit of chromatin, package and regulate expression of eukaryotic genomes. Although the structure of the intact nucleosome has been studied, little was known about structures of its partially unwrapped, transient intermediates. In first part of the project, we presented 9 cryo EM structures of distinct conformations of nucleosome and subnucleosome particles. Our structures show that initial DNA breathing induces conformational changes in the histone octamer, particularly in histone H3, that propagate through the nucleosome and prevent symmetrical DNA opening. In the second part of the project we addressed how nucleosomes can move on DNA. We presented several nucleosome structures showing histone proteins and DNA in different organizational states. We observed that the histone octamer undergoes conformational changes that distort the overall nucleosome structure. As such, rearrangements in the histone core α-helices and DNA induce strain that distorts and moves DNA at SHL 2. Distortion of the nucleosome structure detaches histone α-helices from the DNA, leading to their rearrangement and DNA translocation. In the third part we addressed how nucleosomes interact. The long linear chromatin molecule is extensively condensed to fit DNA inside the nucleus. How distant nucleosomes interact to build tertiary chromatin structure remained elusive. Our structures show that NCP pairs can adopt multiple conformations, but, commonly, two NCPs are oriented with the histone octamers facing each other. In this conformation, the dyad of both nucleosome core particles is facing the same direction, however, the NCPs are laterally shifted and tilted. The histone octamer surface and histone tails in trans NCP pairs remain accessible to regulatory proteins. The overall conformational flexibility of the NCP pair suggests that chromatin tertiary structure is dynamic and allows access of various chromatin modifying machineries to nucleosomes. In summary, our data reveal intrinsic plasticity of the nucleosome, which is exploited by chromatin remodelers and might be used by other chromatin machineries.
Projektbezogene Publikationen (Auswahl)
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Histone octamer rearranges to adapt to DNA unwrapping. Nature Structural & Molecular Biology, 25(1), 101-108.
Bilokapic, Silvija; Strauss, Mike & Halic, Mario
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Cryo-EM of nucleosome core particle interactions in trans. Scientific Reports, 8(1).
Bilokapic, Silvija; Strauss, Mike & Halic, Mario
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Structural rearrangements of the histone octamer translocate DNA. Nature Communications, 9(1).
Bilokapic, Silvija; Strauss, Mike & Halic, Mario
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Nucleosome and ubiquitin position Set2 to methylate H3K36. Nature Communications, 10(1).
Bilokapic, Silvija & Halic, Mario
