National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
1R35GM133611
United States
National Science Foundation (NSF, United States)
1942049
United States
Citation
Journal: Nucleic Acids Res / Year: 2021 Title: Structural basis of chromatin regulation by histone variant H2A.Z. Authors: Tyler S Lewis / Vladyslava Sokolova / Harry Jung / Honkit Ng / Dongyan Tan / Abstract: The importance of histone variant H2A.Z in transcription regulation has been well established, yet its mechanism-of-action remains enigmatic. Conflicting evidence exists in support of both an ...The importance of histone variant H2A.Z in transcription regulation has been well established, yet its mechanism-of-action remains enigmatic. Conflicting evidence exists in support of both an activating and a repressive role of H2A.Z in transcription. Here we report cryo-electron microscopy (cryo-EM) structures of nucleosomes and chromatin fibers containing H2A.Z and those containing canonical H2A. The structures show that H2A.Z incorporation results in substantial structural changes in both nucleosome and chromatin fiber. While H2A.Z increases the mobility of DNA terminus in nucleosomes, it simultaneously enables nucleosome arrays to form a more regular and condensed chromatin fiber. We also demonstrated that H2A.Z's ability to enhance nucleosomal DNA mobility is largely attributed to its characteristic shorter C-terminus. Our study provides the structural basis for H2A.Z-mediated chromatin regulation, showing that the increase flexibility of the DNA termini in H2A.Z nucleosomes is central to its dual-functions in chromatin regulation and in transcription.
History
Deposition
Mar 16, 2021
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Header (metadata) release
Sep 29, 2021
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Map release
Sep 29, 2021
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Update
Nov 17, 2021
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Current status
Nov 17, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV Details: Grid was blotted for 5 seconds before plunge freezing.
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Electron microscopy
Microscope
FEI TALOS ARCTICA
Image recording
Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 2 / Number real images: 1970 / Average exposure time: 60.0 sec. / Average electron dose: 33.0 e/Å2
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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