Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory Element

Fatima-Zohra Braikia (1, 2) , Caroline Conte (1, 2) , Mohamed Moutahir (1, 2) , Yves Denizot (1) , Michel Cogné (3, 1) , Ahmed Amine Khamlichi (2)

1 CRIBL - Contrôle de la Réponse Immune B et des Lymphoproliférations
2 IPBS - Institut de pharmacologie et de biologie structurale
3 IUF - Institut Universitaire de France

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 are unknown. Here we show that not only does the 3’ RR affect transcription at distant sites within the IgH variable region, but that 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.

Mots clés: transcription; Eukaryotic gene; B lymphocyte

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Fatima-Zohra Braikia, Caroline Conte, Mohamed Moutahir, Yves Denizot, Michel Cogné, et al.. Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory Element. Molecular and Cellular Biology, 2015, 35 (19), pp.3370-3380. ⟨10.1128/mcb.00509-15⟩. ⟨hal-01501824⟩