Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1α

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The dynamic architecture of chromatin fibers, a key determinant of genome regulation, is poorly understood. Here, we employ multimodal single-molecule Förster resonance energy transfer studies to reveal structural states and their interconversion kinetics in chromatin fibers. We show that nucleosomes engage in short-lived (micro- to milliseconds) stacking interactions with one of their neighbors. This results in discrete tetranucleosome units with distinct interaction registers that interconvert within hundreds of milliseconds. Additionally, we find that dynamic chromatin architecture is modulated by the multivalent architectural protein heterochromatin protein 1α (HP1α), which engages methylated histone tails and thereby transiently stabilizes stacked nucleosomes. This compacted state nevertheless remains dynamic, exhibiting fluctuations on the timescale of HP1α residence times. Overall, this study reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds, allowing the gene regulation machinery to access compact chromatin.

Original languageEnglish
Article number235
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2018
Externally publishedYes

Bibliographical note

Funding Information:
We thank Jun-ichi Nakayama for the CK2 expression plasmid, Nicolas Sambiagio for assistance with sample preparations. We thank Manuel M. Müller, Jeffrey C. Hansen, Wilma K. Olson, and Nicolas Clauvelin for stimulating discussions during the initial phase of this research. This work was supported by the Sandoz Family Foundation, the Swiss National Science Foundation (Grant 31003A_173169), the European Research Council through the Consolidator Grant 2017 chromo-SUMMIT (724022) and EPFL (B. F.), the Boehringer Ingelheim Foundation (S.K.), and the European Research Council through the Advanced Grant 2014 hybridFRET (671208) to C.A.M.S.

Publisher Copyright:
© 2018 The Author(s).

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