Print Email Facebook Twitter Modification of the histone tetramer at the H3-H3 interface impacts tetrasome conformations and dynamics Title Modification of the histone tetramer at the H3-H3 interface impacts tetrasome conformations and dynamics Author Ordu, O. (TU Delft BN/Nynke Dekker Lab; Kavli institute of nanoscience Delft) Kremser, Leopold (Medical University of Innsbruck) Lusser, Alexandra (Medical University of Innsbruck) Dekker, N.H. (TU Delft BN/Nynke Dekker Lab; Kavli institute of nanoscience Delft) Date 2018 Abstract Nucleosomes consisting of a short piece of deoxyribonucleic acid (DNA) wrapped around an octamer of histone proteins form the fundamental unit of chromatin in eukaryotes. Their role in DNA compaction comes with regulatory functions that impact essential genomic processes such as replication, transcription, and repair. The assembly of nucleosomes obeys a precise pathway in which tetramers of histones H3 and H4 bind to the DNA first to form tetrasomes, and two dimers of histones H2A and H2B are subsequently incorporated to complete the complex. As viable intermediates, we previously showed that tetrasomes can spontaneously flip between a left-handed and right-handed conformation of DNA-wrapping. To pinpoint the underlying mechanism, here we investigated the role of the H3-H3 interface for tetramer flexibility in the flipping process at the single-molecule level. Using freely orbiting magnetic tweezers, we studied the assembly and structural dynamics of individual tetrasomes modified at the cysteines close to this interaction interface by iodoacetamide (IA) in real time. While such modification did not affect the structural properties of the tetrasomes, it caused a 3-fold change in their flipping kinetics. The results indicate that the IA-modification enhances the conformational plasticity of tetrasomes. Our findings suggest that subnucleosomal dynamics may be employed by chromatin as an intrinsic and adjustable mechanism to regulate DNA supercoiling. To reference this document use: http://resolver.tudelft.nl/uuid:60b3d2b4-a74d-4683-8f77-deee5e92543e DOI https://doi.org/10.1063/1.5009100 ISSN 0021-9606 Source Journal of Chemical Physics, 148 (12) Bibliographical note Accepted Author Manuscript Part of collection Institutional Repository Document type journal article Rights © 2018 O. Ordu, Leopold Kremser, Alexandra Lusser, N.H. Dekker Files PDF IA_treated_Tetrasomes_Sup ... terial.pdf 4.46 MB Close viewer /islandora/object/uuid:60b3d2b4-a74d-4683-8f77-deee5e92543e/datastream/OBJ/view