Selective unfolding of erythroid chromatin in the region of the active β-globin gene

Abstract

Globin gene expression, which occurs exclusively in the erythroid cell lineage, is controlled at the level of transcription¹. It is thus of some considerable interest to compare the chromatin structure of this gene with that of inactive genes in erythroid cell nuclei and to compare the chromatin structure of the globin gene in its active and inactive states in nuclei of different cell types. Other workers have observed that globin genes in erythroid cell nuclei exhibit the enhanced overall sensitivity to nucleases² and the hypersensitive site in the 5′-flanking sequence³ typical of many active genes⁴. The nature of the structural changes giving rise to nuclease sensitivity are however obscure. We have investigated the local higher order structure of chromatin in the region of unique genes in chicken by sucrose gradient sedimentation of chromatin restriction fragments. We find that ovalbumin and α2-collagen gene fragments in erythrocyte chromatin and an adult β-globin gene fragment in spleen chromatin sediment with bulk chromatin fragments of the same DNA size, whereas the β-globin gene fragment in erythrocyte chromatin sediments more slowly than bulk fragments of equivalent size. The simplest interpretation of the results is that the solenoid structure in the region of the globin gene is selectively and permanently unfolded on gene activation.