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

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.
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