8YBK

Cryo-EM structure of the human nucleosome containing the H3.1 E97K mutant

Summary for 8YBK

• Entry DOI: 10.2210/pdb8ybk/pdb
• Related: 8YBJ
• EMDB information: 39119 39120
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (6 entities in total)
• Functional Keywords: chromatin, nucleosome, gene regulation, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 201635.15

Authors

Kimura, T.,Hirai, S.,Kujirai, T.,Ogasawara, M.,Takizawa, Y.,Kurumizaka, H. (deposition date: 2024-02-14, release date: 2024-07-24, Last modification date: 2024-09-11)

Primary citation

Kimura, T.,Hirai, S.,Kujirai, T.,Fujita, R.,Ogasawara, M.,Ehara, H.,Sekine, S.I.,Takizawa, Y.,Kurumizaka, H.
Cryo-EM structure and biochemical analyses of the nucleosome containing the cancer-associated histone H3 mutation E97K.
Genes Cells, 29:769-781, 2024

PubMed Abstract: 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.

PubMed: 38972377
DOI: 10.1111/gtc.13143

Experimental method

ELECTRON MICROSCOPY (2.69 Å)