title: Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).
abstract: The transcription of the murine Ig heavy chain locus is regulated not only by the intronic enhancer, E mu, but also by a 3' regulatory region located downstream of the C alpha membrane exon. Several DNase I-hypersensitive sites (hs1-4) and enhancer elements (e.g., C alpha3'E) have been identified in this 3' regulatory region, and some of these were suggested to comprise a locus control region. However, little is known about the coordinate regulation or function of these individual elements. Here we provide evidence that C alpha3'E and hs3 are virtually mirror images of each other and demarcate the edges of an approximately 25-kb region of quasi-dyad symmetry with 3'alphaE(hs1,2) at its center. Flanking 3'alphaE(hs1,2) are inverted repeats and families of repetitive sequences uniquely located in this region. We have observed that, like 3'alphaE(hs1,2) and hs3, C alpha3'E is DNase I hypersensitive in plasma cell lines, but not in a pre-B cell line. Additionally, we found that C alpha3'E and hs3 show significant transcriptional synergy in transfection assays only in a plasma cell line. The DNA topology of the 3' regulatory region coupled with new and existing data on the activity of its individual enhancers during B cell differentiation lead us to propose a biphasic model for the activity of this region. According to our model, one unit, consisting of the 3'-most enhancer, hs4, is active early and throughout B cell development. The second unit, which comprises C alpha3'E, 3'alphaE(hs1,2), and hs3, becomes active later in development, when it contributes to such processes as class switching and increased levels of Ig heavy chain gene transcription in plasma cells.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: S
authors.initials: S
authors.lastname: Saleque
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: R D
authors.initials: RD
authors.lastname: Little
authors.forename: S L
authors.initials: SL
authors.lastname: Giannini
authors.forename: J S
authors.initials: JS
authors.lastname: Michaelson
authors.forename: B K
authors.initials: BK
authors.lastname: Birshtein
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018983:DNA Footprinting; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic