title: LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.
abstract: The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LCR holocomplex, or both. To distinguish between these possibilities, human β-globin locus yeast artificial chromosome (β-YAC) lines were produced in which the ε-globin gene was replaced with a second marked β-globin gene (β(m)), coupled to an intact LCR, a 5'HS3 complete deletion (5'ΔHS3) or a 5'HS3 core deletion (5'ΔHS3c). The 5'ΔHS3c mice expressed β(m)-globin throughout development; γ-globin was co-expressed in the embryonic yolk sac, but not in the fetal liver; and wild-type β-globin was co-expressed in adult mice. Although the 5'HS3 core was not required for β(m)-globin expression, previous work showed that the 5'HS3 core is necessary for ε-globin expression during embryonic erythropoiesis. A similar phenotype was observed in 5'HS complete deletion mice, except β(m)-globin expression was higher during primitive erythropoiesis and γ-globin expression continued into fetal definitive erythropoiesis. These data support a site specificity model of LCR HS-globin gene interaction.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. kpeterson@kumc.edu
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Peterson
authors.forename: Halyna
authors.initials: H
authors.lastname: Fedosyuk
authors.forename: Susanna
authors.initials: S
authors.lastname: Harju-Baker
mesh_terms: D000818:Animals; D002843:Chromatin; D004920:Erythropoiesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D015533:Transcriptional Activation; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D055544:beta-Globins