Developmental stage differences in chromatin subdomains of the β-globin locus

The mammalian beta-globin loci each contain a family of developmentally expressed genes, and a far upstream regulatory element, the locus control region (LCR). In adult murine erythroid cells, the LCR and the transcribed beta-globin genes exist within domains of histone acetylation and RNA polymerase II (pol II) is associated with them. In contrast, the silent embryonic genes lie between these domains within hypoacetylated chromatin, and pol 11 is not found there. We used chromatin immunoprecipitation and real-time PCR to analyze histone modification and pol 11 recruitment to the globin locus in human erythroid K562 cells that express the embryonic E-globin gene but not the adult beta-globin gene. H3 and H4 acetylation and H3 K4 methylation were continuous over a 17-kb region including the LCR and the active E-globin gene. The level of modification varied directly with the transcription of the E-globin gene. In contrast, this region in nonerythroid HeLa cells lacked these modifications and displayed instead widespread H3 K9 methylation. pol 11 was also detected continuously from the LCR to the e-globin gene. These studies reveal several aspects of chromatin structure and pol 11 distribution that distinguish the globin locus at embryonic and adult stages and suggest that both enhancer looping and tracking mechanisms may contribute to LCR-promoter communication at different developmental stages.