An embryonic stage-specific enhancer within the murine ?-globin locus mediates domain-wide histone hyperacetylation.

ABSTRACT: In mammalian nuclei, a select number of tissue-specific gene loci exhibit broadly distributed patterns of histone modifications, such as histone hyperacetylation, that are normally associated with active gene promoters. Previously, we characterized such hyperacetylated domains within mammalian ?-globin gene loci, and determined that within the murine locus, neither the ?-globin locus control region nor the gene promoters were required for domain formation. Here, we identify a developmentally specific erythroid enhancer, hypersensitive site-embryonic 1 (HS-E1), located within the embryonic ?-globin domain in mouse, which is homologous to a region located downstream of the human embryonic ?-globin gene. This sequence exhibits nuclease hypersensitivity in primitive erythroid cells and acts as an enhancer in gain-of-function assays. Deletion of HS-E1 from the endogenous murine ?-globin locus results in significant decrease in the expression of the embryonic ?-globin genes and loss of the domain-wide pattern of histone hyperacetylation. The data suggest that HS-E1 is an enhancer that is uniquely required for ?-like globin expression in primitive erythroid cells, and that it defines a novel class of enhancer that works in part by domain-wide modulation of chromatin structure.

SUBMITTER: Fromm G 

PROVIDER: S-EPMC3109543 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature