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

Blood | May 12, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21321362

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.

Pubmed ID: 21321362 RIS Download

Mesh terms: Acetylation | Animals | Chromatin Immunoprecipitation | Embryo, Mammalian | Enhancer Elements, Genetic | Erythroid Cells | Gene Expression | Gene Expression Regulation, Developmental | Histones | Mice | Reverse Transcriptase Polymerase Chain Reaction | beta-Globins

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK054071
  • Agency: NIDDK NIH HHS, Id: R01 DK070687
  • Agency: NIGMS NIH HHS, Id: T32 GM068411
  • Agency: NIGMS NIH HHS, Id: T32 GM068411

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