The Role of Histone Variants in Cancer

In eukaryotes, chromosomal DNA is packaged around histone proteins into tightly coiled structures, called nucleosomes, which then form further repeating condensed elements. This fundamental repeating unit, chromatin, ensures that the large eukaryotic genome can pack into the nucleus while still allowing gene expression. Specific mechanisms have evolved to regulate access to DNA by the proteins that control gene expression, such as transcription factors and polymerases, and to control the looping structure of the chromatin to allow interaction between distant DNA locations. One of the major mechanisms by which this is achieved is by insertion of variant histones, which provide different degrees of open chromatin structure compared to canonical proteins. A further mechanism that can alter control of gene expression is the post-translational modification of histone proteins, which not only physically alter chromatin structure but also recruit remodelling enzymes that reposition nucleosomes. This chapter describes the various histone variants and modifications that control chromatin structure and highlight how these modifications can alter transcription. These histone variants can be altered in disease states; alterations that occur in cancer will then be briefly outlined.