title: An embryonic stage-specific enhancer within the murine β-globin locus mediates domain-wide histone hyperacetylation.
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.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Center for Pediatric Biomedical Research, Rochester, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Fromm
authors.forename: Brenda
authors.initials: B
authors.lastname: Cadiz-Rivera
authors.forename: Christina
authors.initials: C
authors.lastname: de Vries
authors.forename: Michael
authors.initials: M
authors.lastname: Getman
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: McGrath
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kingsley
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fields
authors.forename: Steven
authors.initials: S
authors.lastname: Fiering
authors.forename: Michael
authors.initials: M
authors.lastname: Bulger
mesh_terms: D000107:Acetylation; D000818:Animals; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D041905:Erythroid Cells / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055544:beta-Globins / Q000235:genetics*
chemical_list: D006657:Histones; D055544:beta-Globins