Higher concentrations of histone macroH2A in the Barr body are correlated with higher nucleosome density

Histone macroH2A, which is a subtype of histone H2A, possesses a histone H2 A-like portion fused to a relatively long non-histone portion. MacroH2A has been shown to associate preferentially with the inactive X chromosome [1], To investigate the specificity of this association, the nuclear distributi on of macroH2A was compared with that of regular core histones, In normal h uman female fibroblasts, all anti-histone antibodies that were tested (incl uding anti-macroH2A antibody) preferentially labeled the inactive X chromos ome. Moreover, when expressed as green fluorescent protein (GFP) fusions, b oth histone H2A and macroH2A were concentrated in the Barr body. These data clearly show the presence of a higher density of nucleosomes in the inacti ve X chromosome. Accordingly, the specificity of the macroH2A association w ith the inactive X chromosome should be reconsidered. While investigating t he role of macroH2A, we found that the proximity of the non-histone region of macroH2A to a promoter could lead to a specific repression of transcript ion, suggesting that the incorporation of macroH2A into chromatin might hel p to establish the stable pattern of gene expression in differentiated cell s.