MACROH2A2, a New Member of the MACROH2A Core Histone Family

MACROH2As are core histones that have a unique hybrid structure consisting of an amino-terminal domain that closely resembles a full-length histone H2A followed by a large nonhistone region. The human MACROH2A1 gene, on chromosome 5, encodes two MACROH2A subtypes, MACROH2A1.1 and MACROH2A1.2, produced by alternate splicing. Here we report the identification of MACROH2A2, a new MACROH2A subtype encoded by a separate gene on human chromosome 10, MACROH2A2. The amino acid sequence of human MACROH2A2 is 68% identical to human MACROH2A1.2. We show by immunofluorescence on mouse tissue sections that MACROH2A2, like MACROH2A1.2, is concentrated in the inactive X chromosome. However, MACROH2A2 has a very different pattern of expression in the cell types present in the liver and kidney. When MACROH2A2 and MACROH2A1.2 are present in the same nucleus, they have a similar, though nonidentical, pattern of localization, with both subtypes present in the inactive X chromosome. Our results suggest a developmental role for MACROH2A subtypes.