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Blood. 2011 May 12;117(19):5207-14. doi: 10.1182/blood-2010-08-302018. Epub 2011 Feb 14.

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

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  • 1Department of Pediatrics, University of Rochester Medical Center, Center for Pediatric Biomedical Research, Rochester, NY, USA.

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 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.

PMID:
21321362
[PubMed - indexed for MEDLINE]
PMCID:
PMC3109543
Free PMC Article

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