title: Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory Element.
abstract: Eukaryotic gene expression is often controlled by distant regulatory elements. In developing B lymphocytes, transcription is associated with V(D)J recombination at immunoglobulin loci. This process is regulated by remote cis-acting elements. At the immunoglobulin heavy chain (IgH) locus, the 3' regulatory region (3'RR) promotes transcription in mature B cells. This led to the notion that the 3'RR orchestrates the IgH locus activity at late stages of B cell maturation only. However, long-range interactions involving the 3'RR were detected in early B cells, but the functional consequences of these interactions were unknown. Here we show that not only does the 3'RR affect transcription at distant sites within the IgH variable region but also it conveys a transcriptional silencing activity on both sense and antisense transcription. The 3'RR-mediated silencing activity is switched off upon completion of VH-DJH recombination. Our findings reveal a developmentally controlled, stage-dependent shift in the transcriptional activity of a master regulatory element.
authors.affiliation: CNRS UMR5089, Institut de Pharmacologie et de Biologie Structurale (IPBS), FRBT, Toulouse, France Université de Toulouse, UPS, IPBS, Toulouse, France.
authors.forename: Fatima-Zohra
authors.initials: FZ
authors.lastname: Braikia
authors.affiliation: CNRS UMR5089, Institut de Pharmacologie et de Biologie Structurale (IPBS), FRBT, Toulouse, France Université de Toulouse, UPS, IPBS, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Conte
authors.affiliation: CNRS UMR5089, Institut de Pharmacologie et de Biologie Structurale (IPBS), FRBT, Toulouse, France Université de Toulouse, UPS, IPBS, Toulouse, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Moutahir
authors.affiliation: CNRS UMR 7276, Limoges, France Université de Limoges, Limoges, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
authors.affiliation: CNRS UMR 7276, Limoges, France Université de Limoges, Limoges, France Institut Universitaire de France, Limoges, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.affiliation: CNRS UMR5089, Institut de Pharmacologie et de Biologie Structurale (IPBS), FRBT, Toulouse, France Université de Toulouse, UPS, IPBS, Toulouse, France ahmed.khamlichi@ipbs.fr.
authors.forename: Ahmed Amine
authors.initials: AA
authors.lastname: Khamlichi
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D050436:Regulatory Elements, Transcriptional; D014158:Transcription, Genetic; D060152:V(D)J Recombination
chemical_list: D007143:Immunoglobulin Heavy Chains