Histone variants replace the core histones in a substantial fraction of 
nucleosomes, affecting chromatin structure and impacting chromatin-templated 
processes. In many instances incorporation of histone variants results in 
formation of specialized regions of chromatin. Proper localization of histone 
variants to distinct regions of the genome is critical for their function, yet 
how this specific localization is achieved remains unclear. macroH2A1 is 
enriched on the inactive X chromosome in female mammalian cells, where it 
functions to maintain gene silencing. macroH2A1 consists of a histone H2A-like 
histone domain and a large, globular C-terminal macro domain that is not present 
in other histone proteins. The histone domain of macroH2A1 is alone sufficient 
to direct enrichment on the inactive X chromosome when expressed in female 
cells, indicating that sequences important for correct localization lie in this 
domain. Here we investigate whether divergent sequences of the H2A variant 
macroH2A1 contribute to its correct localization. We mapped the regions of the 
macroH2A1 histone domain that are sufficient for localization to the inactive X 
chromosome using chimeras between H2A and the histone domain of macroH2A1. 
Multiple short sequences dispersed along the macroH2A1 histone domain 
individually supported enrichment on the inactive X chromosome when introduced 
into H2A. These sequences map to the surface of the macroH2A1/H2B dimer, but are 
buried in the crystal structure of the macroH2A1 containing nucleosome, 
suggesting that they may contribute to recognition by macroH2A1/H2B deposition 
factors.