Histone acetylation at the human P-globin locus changes with developmental age

To delineate the relationship between epigenetic modifications and hemoglobin switching, we compared the pattern of histone acetylation and pol II binding across the P-globin locus at fetal and adult stages of human development. To make this comparison possible, we introduced an external control into experimental samples in chromatin immunoprecipitation (Chip) assays. Using this common standard, we found that the locus control region (LCR) was acetylated to the same level at all stages, whereas acetylation levels at the individual gene regions correlated with the state of transcription. In the active genes, the promoters were less acetylated compared with the coding regions. Furthermore, all globin promoters were acetylated to a similar level irrespective of the state of transcription. However, after correction for the loss of nucleosomes, the level of acetylation per histone at the active 7 and P promoters was 5- to 7-fold greater than that at the inactive epsilon promoter. Although the histone acetylation level within the LCR was developmentally stable, pol II binding in fetal erythroblasts was 2- to 3-fold greater than that in adult erythroblasts. These results demonstrate that dynamic changes in histone acetylation and pol R take place as the human P-globin gene region undergoes its developmental switches.