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

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

Authors

  • Fromm G
  • Cadiz-Rivera B
  • de Vries C
  • Getman M
  • McGrath KE
  • Kingsley PD
  • Fields J
  • Fiering S
  • Bulger M

Journal

Blood

Publication Data

May 12, 2011

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

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