Histone H3.3 G34 Mutations Alter Histone H3K36 and H3K27 Methylation In Cis

Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive studies on K27M and K36M mutations, little is known about the mechanism of G34 mutations found in pe...

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Published inJournal of molecular biology Vol. 430; no. 11; pp. 1562 - 1565
Main Authors Shi, Leilei, Shi, Jiejun, Shi, Xiaobing, Li, Wei, Wen, Hong
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 25.05.2018
Subjects
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
brain
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Child
Epigenesis, Genetic
G34 mutations
genes
Giant Cell Tumor of Bone - genetics
Giant Cell Tumor of Bone - metabolism
giant cell tumor of the bone
giant cells
glioblastoma
Glioblastoma - genetics
Glioblastoma - metabolism
HeLa Cells
histone variant H3.3
histones
Histones - chemistry
Histones - genetics
Humans
Lysine - chemistry
Methylation
Mutation
SETD2
SETD2
GBM
G34 mutations
giant cell tumor of the bone
WT
histone variant H3.3
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Summary:Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive studies on K27M and K36M mutations, little is known about the mechanism of G34 mutations found in pediatric glioblastoma or giant cell tumors of the bone. Here we report that unlike the K27M or K36M that affect global histone methylation, the giant cell tumors of the bone G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis), a mechanism distinct from known histone mutations. [Display omitted] •Giant cell tumors of the bone (GCTB) H3.3G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis).•GCTB H3.3G34 mutations (G34L/W) inhibits SETD2 enzymatic activity.•GCTB H3.3G34 mutations (G34L/W) do not affect the enzymatic activity of EZH2 or p300.•GCTB H3.3G34 mutations (G34L/W) affect histone H3K36 and H3K27 methylation readers binding to chromatin.
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These authors contribute equally to this paper.
ISSN:0022-2836
1089-8638
1089-8638
DOI:10.1016/j.jmb.2018.04.014