Year: 2021
Type: article
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 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.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkab907
Institutions: Stony Brook University, Rockefeller University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: National Science Foundation, U.S. Department of Energy, Oregon Health and Science University, Environmental Molecular Sciences Laboratory, University of Toronto, Stony Brook University, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Biological and Environmental Research
Awards: Dynamics and Regulation of Chromatin in DNA Metabolism, G1213529597, G2165894320, G3021579539, G3634906849, CAREER: Regulation of Chromatin by Histone Variants, G4090771277, A 200KV CRYO-TEM FOR IMAGING BIOLOGICAL STRUCTURES, G4429615956, G4565997878, Pacific Northwest Center for Cryo-EM, G6472479345, G7339355041
OpenAlex ID: W3207804469