title: Characterization of a Schwann cell enhancer in the myelin basic protein gene.
abstract: Oligodendrocytes and Schwann cells use diverse regulatory elements to transcribe myelin basic protein (Mbp). For example, an enhancer 9.0 kb upstream of Mbp (MbpSCE1) activated either the proximal Mbp or hsp68 promoters only in Schwann cells in transgenic mice. Here, we analyze MbpSCE1 in vitro and in vivo and show that MbpSCE1 also activates another myelin gene, Mpz, specifically in Schwann cells in transgenic mice. Surprisingly, although MbpSCE1 behaves as an enhancer in Schwann cells, we show here for the first time that it also activates transcription robustly in cultured oligodendrocytes, but only from its original genomic position. Diverse nuclear proteins binding at distinct combinations of DNA elements in the two cell types may account for cell-specific MbpSCE1 function. A further surprise is that MbpSCE1 activation does not depend on consensus binding sites for the myelin-associated PPARbeta or Krox 20 transcription factors. Finally, chromatin context augments activation of MbpSCE1. Therefore, MbpSCE1 is active in both Schwann cells and oligodendrocytes, but by diverse mechanisms.
authors.affiliation: San Raffaele Scientific Institute, DIBIT, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
authors.forename: Antonella
authors.initials: A
authors.lastname: Pizzagalli
authors.forename: Ernesta
authors.initials: E
authors.lastname: Fagiani
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D018983:DNA Footprinting; D003850:Deoxyribonuclease I; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D002843:Chromatin; D004676:Myelin Basic Protein; D009687:Nuclear Proteins; D003850:Deoxyribonuclease I