Coordinated DNA and histone dynamics drive accurate histone H2A.Z exchange.

Autor: Poyton MF; Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA., Feng XA; Department of Biology, Johns Hopkins University, Baltimore, MD, USA.; Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA., Ranjan A; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Lei Q; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Wang F; Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Zarb JS; Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA., Louder RK; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Park G; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Jo MH; Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA., Ye J; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Liu S; Department of Biology, Johns Hopkins University, Baltimore, MD, USA., Ha T; Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Howard Hughes Medical Institute, Baltimore, MD, USA., Wu C; Department of Biology, Johns Hopkins University, Baltimore, MD, USA.; Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Mar 11; Vol. 8 (10), pp. eabj5509. Date of Electronic Publication: 2022 Mar 09.
DOI: 10.1126/sciadv.abj5509
Abstrakt: Nucleosomal histone H2A is exchanged for its variant H2A.Z by the SWR1 chromatin remodeler, but the mechanism and timing of histone exchange remain unclear. Here, we quantify DNA and histone dynamics during histone exchange in real time using a three-color single-molecule FRET assay. We show that SWR1 operates with timed precision to unwrap DNA with large displacement from one face of the nucleosome, remove H2A-H2B from the same face, and rewrap DNA, all within 2.3 s. This productive DNA unwrapping requires full SWR1 activation and differs from unproductive, smaller-scale DNA unwrapping caused by SWR1 binding alone. On an asymmetrically positioned nucleosome, SWR1 intrinsically senses long-linker DNA to preferentially exchange H2A.Z on the distal face as observed in vivo. The displaced H2A-H2B dimer remains briefly associated with the SWR1-nucleosome complex and is dissociated by histone chaperones. These findings reveal how SWR1 coordinates DNA unwrapping with histone dynamics to rapidly and accurately place H2A.Z at physiological sites on chromatin.
Databáze: MEDLINE