Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant

MacroH2A1 is an unusual variant of the core histone H2A which is enriched i n chromatin on the inactive X chromosome of female mammals. The N-terminal third of the protein shares 65% amino acid identity with core histone H2A, while the remaining two-thirds of the protein are novel, with a small stret ch of basic amino acids and a putative leucine zipper motif, We have now cl oned a second macroH2A gene, encoding macroH2A2 which shares 80% amino acid identity with macroH2A1, Despite mapping to different chromosomes, the gen omic organization of the macroH2A2 and macroH2A1 genes are nearly identical , The leucine zipper motif of macroH2A1 is not conserved in macroH2A2. Like macroH2A1, macroH2A2 forms a Macro Chromatin Body in the nuclei of female cells which is coincident with an X chromosome and co-localizes with macroH 2A1, To address the distribution of other histone H2A variants in relation to macroH2A and the inactive X chromosome, we constructed a series of epito pe-tagged versions of other histone H2A variants, Like the recently describ ed H2A-Bbd (Barr body-deficient) variant, the histone variant H2A.Z was fou nd to be deficient in chromatin on the inactive X chromosome in a significa nt proportion of female nuclei. This study provides further information abo ut the nucleosomal composition of chromatin on the inactive X chromosome an d indicates that a number of H2A variants are non-randomly distributed on t he active and inactive X chromosomes.