title: The chromatin "landscape" of a murine adult β-globin gene is unaffected by deletion of either the gene promoter or a downstream enhancer.
abstract: In mammals, the complex tissue- and developmental-specific expression of genes within the β-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regulation of chromatin structure and gene expression within the cluster is not fully defined. To further elucidate regulation of the adult β-globin genes, we investigate the effects of two deletions engineered within the endogenous murine β-globin locus. First, we find that deletion of the β2-globin gene promoter, while eliminating β2-globin gene expression, results in no additional effects on chromatin structure or gene expression within the cluster. Notably, our observations are not consistent with competition among the β-globin genes for LCR activity. Second, we characterize a novel enhancer located 3' of the β2-globin gene, but find that deletion of this sequence has no effect whatsoever on gene expression or chromatin structure. This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin "landscape" or even by functional assays.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center and Center for Pediatric Biomedical Research, Rochester, New York, United States of America.
authors.forename: Brenda
authors.initials: B
authors.lastname: Cadiz-Rivera
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center and Center for Pediatric Biomedical Research, Rochester, New York, United States of America; National Institute for Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Fromm
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center and Center for Pediatric Biomedical Research, Rochester, New York, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: de Vries
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fields
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center and Center for Pediatric Biomedical Research, Rochester, New York, United States of America.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: McGrath
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Fiering
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center and Center for Pediatric Biomedical Research, Rochester, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Bulger
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D019901:Locus Control Region / Q000235:genetics; D008297:Male; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D055544:beta-Globins / Q000235:genetics*
chemical_list: D002843:Chromatin; D055544:beta-Globins