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TitleCryo-EM structure and biochemical analyses of the nucleosome containing the cancer-associated histone H3 mutation E97K.
Journal, issue, pagesGenes Cells, Vol. 29, Issue 9, Page 769-781, Year 2024
Publish dateJul 7, 2024
AuthorsTomoaki Kimura / Seiya Hirai / Tomoya Kujirai / Risa Fujita / Mitsuo Ogasawara / Haruhiko Ehara / Shun-Ichi Sekine / Yoshimasa Takizawa / Hitoshi Kurumizaka /
PubMed AbstractThe Lys mutation of the canonical histone H3.1 Glu97 residue (H3E97K) is found in cancer cells. Previous biochemical analyses revealed that the nucleosome containing the H3E97K mutation is extremely ...The Lys mutation of the canonical histone H3.1 Glu97 residue (H3E97K) is found in cancer cells. Previous biochemical analyses revealed that the nucleosome containing the H3E97K mutation is extremely unstable as compared to the wild-type nucleosome. However, the mechanism by which the H3E97K mutation causes nucleosome instability has not been clarified yet. In the present study, the cryo-electron microscopy structure of the nucleosome containing the H3E97K mutation revealed that the entry/exit DNA regions of the H3E97K nucleosome are disordered, probably by detachment of the nucleosomal DNA from the H3 N-terminal regions. This may change the intra-molecular amino acid interactions with the replaced H3 Lys97 residue, inducing structural distortion around the mutated position in the nucleosome. Consistent with the nucleosomal DNA end flexibility and the nucleosome instability, the H3E97K mutation exhibited reduced binding of linker histone H1 to the nucleosome, defective activation of PRC2 (the essential methyltransferase for facultative heterochromatin formation) with a poly-nucleosome, and enhanced nucleosome transcription by RNA polymerase II.
External linksGenes Cells / PubMed:38972377 / PubMed Central
MethodsEM (single particle)
Resolution2.38 - 2.69 Å
Structure data

EMDB-39119, PDB-8ybj:
Cryo-EM structure of human nucleosome core particle composed of the Widom 601 DNA sequence
Method: EM (single particle) / Resolution: 2.38 Å

EMDB-39120, PDB-8ybk:
Cryo-EM structure of the human nucleosome containing the H3.1 E97K mutant
Method: EM (single particle) / Resolution: 2.69 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / chromatin / nucleosome / gene regulation / DNA BINDING PROTEIN-DNA COMPLEX

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