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

Department of Pediatrics, University of Rochester Medical Center, Center for Pediatric Biomedical Research, Rochester, NY, USA.
Blood (Impact Factor: 10.45). 02/2011; 117(19):5207-14. DOI: 10.1182/blood-2010-08-302018
Source: PubMed


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 β-globin gene loci, and determined that within the murine locus, neither the β-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 β-globin domain in mouse, which is homologous to a region located downstream of the human embryonic ε-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 β-globin locus results in significant decrease in the expression of the embryonic β-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 β-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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Available from: Steven N Fiering, Feb 26, 2014
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    • "Notably, two distinct hyperacetylated domains occur over the β1- and β2-globin genes, and are present in both primitive and definitive erythroid cells and qualitatively identical in both despite the dramatic difference in expression levels of these genes between the two stages. Deletion of previously identified control sequences, including the LCR and HS-E1, has no effect on chromatin structure in the vicinity of the adult β1- or β2-globin genes [6], [12], [14]. The identity of cis-acting DNA sequences involved in the establishment and maintenance of these domains remains obscure. "
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