An embryonic stage–specific enhancer within the murine β-globin locus mediates domain-wide histone hyperacetylation
| Autor: | Michael Bulger, Michael Getman, Paul D. Kingsley, Steven Fiering, Kathleen E. McGrath, Jennifer Fields, George Fromm, Brenda Cadiz-Rivera, Christina de Vries |
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| Rok vydání: | 2011 |
| Předmět: |
Chromatin Immunoprecipitation
Immunology Gene Expression Locus (genetics) beta-Globins Biochemistry Histones Mice Red Cells Iron and Erythropoiesis Erythroid Cells hemic and lymphatic diseases Animals Enhancer trap Enhancer Locus control region Regulation of gene expression biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Acetylation Cell Biology Hematology Embryo Mammalian Molecular biology Chromatin Enhancer Elements Genetic Histone biology.protein Chromatin immunoprecipitation |
| Zdroj: | Blood. 117:5207-5214 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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