Multiple facets of the unique histone variant macroH2A: from genomics to cell biology

Histone variants replace canonical histones in nucleosomes to designate regions of chromatin for specific purposes. MacroH2A is a large histone variant distinguished by a ~30 kDa carboxyl-terminal macro domain. The association of macroH2A with the inactive X chromosome in female mammals has led to the hypothesis that macroH2A is involved in heterochromatin-associated transcriptional repression. Here we review data from a number of laboratories that suggest the role of macroH2A in regulating gene expression is, in fact, more complex. For example, macroH2A can play either a positive or negative role in transcriptional regulation in a context-dependent manner. Additionally, macroH2A has been linked to the control of the cell cycle and cell proliferation. We also describe areas where further research is required to extend our knowledge about this enigmatic histone variant.