Identification of a conserved erythroid specific domain of histone acetylation across the alpha-globin gene cluster

We have analyzed the pattern of core histone acetylation across 250 kb of t he telomeric region of the short arm of human chromosome 16. This gene-dens e region, which includes the a-globin genes and their regulatory elements e mbedded within widely expressed genes, shows marked differences in histone acetylation between erythroid and non-erythroid cells. In non-erythroid cel ls, there was a uniform 2- to 3-fold enrichment of acetylated histones, com pared with heterochromatin, across the entire region. In erythroid cells, a n approximate to 100-kb segment of chromatin encompassing the a genes and t heir remote major regulatory element was highly enriched in histone H4 acet ylated at Lys-5. Other lysines in the N-terminal tail of histone H4 showed intermediate and variable levels of enrichment. Similar broad segments of e rythroid-specific histone acetylation were found in the corresponding synte nic regions containing the mouse and chicken a-globin gene clusters. The bo rders of these regions of acetylation are located in similar positions in a ll three species, and a sharply defined 3' boundary coincides with the prev iously identified breakpoint in conserved synteny between these species. We have therefore demonstrated that an erythroid-specific domain of acetylati on has been conserved across several species, encompassing not only the a-g lobin genes but also a neighboring widely expressed gene. These results con trast with those at other clusters and demonstrate that not all genes are o rganized into discrete regulatory domains.