THE INACTIVE X-CHROMOSOME IN FEMALE MAMMALS IS DISTINGUISHED BY A LACK OF HISTONE-H4 ACETYLATION, A CYTOGENETIC MARKER FOR GENE-EXPRESSION

We have immunolabeled human and mouse metaphase chromosomes with antib odies specific for the acetylated isoforms of histone H4. All chromoso mes were labeled in regions corresponding to conventional R bands (reg ions enriched in coding DNA), except for a single chromosome in female cells, which was largely unlabeled and which we have identified as th e inactive X (Xi). Three sharply defined immunofluorescent bands, enha nced by butyrate pretreatment, were observed in homologous positions o n the human and mouse Xi, showing limited, regional persistence of H4 acetylation. Two of these bands are in cytogenetic regions known to co ntain genes expressed on Xi. We propose that H4 hyperacetylation defin es regions of the genome containing potentially transcriptionally acti ve chromatin, while virtual absence of H4 acetylation defines both con stitutive and facultative heterochromatin.