Review Volume 9, Issue 3 pp 602—614
The histone variant H3.3 claims its place in the crowded scene of epigenetics
Figure 1. (A) Sequence alignment comparing the differences in the amino acids of H3.3 in five species. In red: the evolutionarily conserved amino acids that, along with Ala87, coordinate the binding to dedicated histone chaperones. (B) Annotated somatic mutations in H3F3A and H3F3B causally linked to tumours in humans. (C) Regulation of histone H3 pool in the cell. i) Newly synthesised histone proteins H3 and H4 ii) associate with Hsc70 and Hsp90, which determine the stability and degradation rate of H3-H4 dimers. In the nucleus, the binding to NASP controls the supply of soluble H3-H4 to ASF1a and ASF1b. H3-H4 dimers are then handed over to ASF1a/b, iii) which then transfers H3.1/2-H4 dimers to CAF-1, iv) whereas ASF1a transfers H3.3-H4 dimers to both HIRA/UBN1/CABN1 and ATRX/DAXX for loading onto the chromatin. v) Schematic overview of histone chaperones binding H3.1/2 and H3.3, from their synthesis to their deposition onto the chromatin.