First Author | Fromm G | Year | 2011 |
Journal | Blood | Volume | 117 |
Issue | 19 | Pages | 5207-14 |
PubMed ID | 21321362 | Mgi Jnum | J:173283 |
Mgi Id | MGI:5013709 | Doi | 10.1182/blood-2010-08-302018 |
Citation | Fromm G, et al. (2011) An embryonic stage-specific enhancer within the murine beta-globin locus mediates domain-wide histone hyperacetylation. Blood 117(19):5207-14 |
abstractText | 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 beta-globin gene loci, and determined that within the murine locus, neither the beta-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 beta-globin domain in mouse, which is homologous to a region located downstream of the human embryonic epsilon-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 beta-globin locus results in significant decrease in the expression of the embryonic beta-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 beta-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. |