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. Author manuscript; available in PMC: 2015 Oct 1.
Published in final edited form as: Semin Radiat Oncol. 2014 Oct;24(4):240–247. doi: 10.1016/j.semradonc.2014.06.003

Figure 2. Hotspot histone mutations occur in nearly 80% of DIPGs and ∼35% of NBS-HGGs.

Figure 2

a. The basic unit of chromatin is the nucleosome; DNA wrapped around a histone octamer consisting of two copies of H2A, H2B, H3, and H4. The N-terminal tails of histones undergo post-translational modifications (PTMs), represented by yellow and blue circles, which in turn alter chromatin accessibility and recruitment of effector proteins, together influencing transcriptional permissiveness. This is accomplished because PTMs can 1) themselves alter the strength of DNA-histone interactions 2) facilitate recruitment of chromatin remodeling complexes or histone PTM-binding effector proteins.

b. p.K27M substitutions occur in histone H3.1 and H3.3; p.G34R/V substitutions occur in H3.3. Histone H3.1/3.3 p.K27M exerts a dominant effect, preventing the accumulation of H3K27me2/3 on the wild-type histone H3 expressed in the same cell. p.G34R/V mutations do not exert the same effect on H3K27me3, but p.K27M and p.G34R/V histone mutations are associated with distinct genome-wide DNA methylation and gene expression tumor signatures.

c. Table summarizing the functional consequences of histone mutations.