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TitleStructural and Biochemical Characterization of the Nucleosome Containing Variants H3.3 and H2A.Z.
Journal, issue, pagesEpigenomes, Vol. 8, Issue 2, Year 2024
Publish dateMay 27, 2024
AuthorsHarry Jung / Vladyslava Sokolova / Gahyun Lee / Victoria Rose Stevens / Dongyan Tan /
PubMed AbstractVariant H3.3, along with H2A.Z, is notably enriched at promoter regions and is commonly associated with transcriptional activation. However, the specific molecular mechanisms through which H3.3 ...Variant H3.3, along with H2A.Z, is notably enriched at promoter regions and is commonly associated with transcriptional activation. However, the specific molecular mechanisms through which H3.3 influences chromatin dynamics at transcription start sites, and its role in gene regulation, remain elusive. Using a combination of biochemistry and cryo-electron microscopy (cryo-EM), we show that the inclusion of H3.3 alone does not induce discernible changes in nucleosome DNA dynamics. Conversely, the presence of both H3.3 and H2A.Z enhances DNA's flexibility similarly to H2A.Z alone. Interestingly, our findings suggest that the presence of H3.3 in the H2A.Z nucleosome provides slightly increased protection to DNA at internal sites within the nucleosome. These results imply that while H2A.Z at active promoters promotes the formation of more accessible nucleosomes with increased DNA accessibility to facilitate transcription, the simultaneous presence of H3.3 offers an additional mechanism to fine-tune nucleosome accessibility and the chromatin environment.
External linksEpigenomes / PubMed:38920622 / PubMed Central
MethodsEM (single particle)
Resolution3.0 Å
Structure data

44148

9b3p

EMDB-44148, PDB-9b3p:
The cryo-EM structure of the H2A.Z-H3.3 double-variant nucleosome
Method: EM (single particle) / Resolution: 3.0 Å

Source
  • Escherichia coli (E. coli)
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • mus musculus (house mouse)
  • synthetic construct (others)
KeywordsSTRUCTURAL PROTEIN/DNA / histone variant / nucleosome / chromatin / complex / STRUCTURAL PROTEIN / STRUCTURAL PROTEIN-DNA complex

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