RT Journal Article
SR Electronic
T1 Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000919
DO 10.26508/lsa.202000919
VO 4
IS 4
A1 Cheng-Han Ho
A1 Yoshimasa Takizawa
A1 Wataru Kobayashi
A1 Yasuhiro Arimura
A1 Hiroshi Kimura
A1 Hitoshi Kurumizaka
YR 2021
UL https://www.life-science-alliance.org/content/4/4/e202000919.abstract
AB SET8 is solely responsible for histone H4 lysine-20 (H4K20) monomethylation, which preferentially occurs in nucleosomal H4. However, the underlying mechanism by which SET8 specifically promotes the H4K20 monomethylation in the nucleosome has not been elucidated. Here, we report the cryo-EM structures of the human SET8–nucleosome complexes with histone H3 and the centromeric H3 variant, CENP-A. Surprisingly, we found that the overall cryo-EM structures of the SET8–nucleosome complexes are substantially different from the previous crystal structure models. In the complexes with H3 and CENP-A nucleosomes, SET8 specifically binds the nucleosomal acidic patch via an arginine anchor, composed of the Arg188 and Arg192 residues. Mutational analyses revealed that the interaction between the SET8 arginine anchor and the nucleosomal acidic patch plays an essential role in the H4K20 monomethylation activity. These results provide the groundwork for understanding the mechanism by which SET8 specifically accomplishes the H4K20 monomethylation in the nucleosome.