Histone H3.3 and chromatin homeostasis
Histone H3 variants such as H3.3 contribute to the definition of chromatin domains. Dedicated histone H3.3 chaperones deposit H3.3 into specific genomic regions such as active genes, regulatory elements and heterochromatin. A form of pediatric gliomas called diffuse intrinsic pontine glioma (DIPG) is caused by mutations in H3.3, among which H3.3K27M is the most prominent. H3.3K27M leads to a global reduction of H3K27me3, but other effects on nuclear organization are not known.
- Mechanisms of H3.3 deposition into chromatin
- Impact of DIPG-causing H3.3 mutations on nuclear architecture
- Identfication of PML-associated domains (PADs); PML modulates H3.3 deposition and is important for maintance of heterochromatin (Debarre et al 2017 Genome Res 27, 913-21)
- Chromatin-bound oncoprotein DEK as gate-keeper of chromatin (Ivanauskiene et al 2014 Genome Res 24, 1584-1594)
- Multi-step targeting process of H3.3 to chromatin via PML bodies prior to loading H3.3 on chromatin (Delbarre et al 2013 Genome Res 23, 440-451)