A conserved, extended chromatin opening within α-globin locus during development

Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine α-globin locus, as well as along the human α-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic ζ-gene and fetal/adult α-genes displayed different developmental patterns. The level of histone modification at ζ-gene was developmentally regulated, in accordance with the level of ζ-gene expression, whereas the α-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Histone deacetylase inhibition selectively increased acetylation at the inactive ζ-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult α-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching.