ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical Journal Année : 2010

ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus

Vasiliki Papadopoulou
  • Fonction : Auteur
Antonio Postigo
  • Fonction : Auteur
Ester Sánchez-Tilló
  • Fonction : Auteur
Andrew C.G. Porter
  • Fonction : Auteur

Résumé

BCL6 is essential for normal antibody responses and is highly expressed in germinal centre B-cells. Constitutive expression due to chromosomal translocations or mutations of cis-acting regulatory elements contributes to diffuse large B-cell lymphoma. BCL6 expression is, therefore, tightly regulated in a lineage and developmental stage specific manner and disruption of normal controls can contribute to lymphomagenesis. In order to discover potential cis-acting control regions we carried out DNase I hypersensitive site mapping. Gel shift assays and chromatin immuno-precipitation of the core region of a hypersensitive site 4.4kb upstream of BCL6 transcription initiation (HSS-4.4) showed an E-box element binding ZEB1 and the co-repressor CtBP. As compared to peripheral blood B-cells, ZEB1, a two-handed zinc finger transcriptional repressor, is expressed at relatively low levels in germinal centre cells whereas BCL6 has the opposite pattern of expression. Transfection of ZEB1 cDNA caused a reduction in BCL6 expression and a mutated ZEB1, incapable of binding CtBP, lacked this effect. siRNA mediated knockdown of ZEB1 or CtBP produced an increase in BCL6 mRNA. We propose that HSS-4.4 is a distal promoter element binding a repressive complex consisting of ZEB1 and CtBP. CtBP is ubiquitously expressed and our results suggest regulation of ZEB1 is required for control of BCL6 expression.

Mots clés

Fichier principal
Vignette du fichier
PEER_stage2_10.1042%2FBJ20091578.pdf (812.62 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00479270 , version 1 (30-04-2010)

Identifiants

Citer

Vasiliki Papadopoulou, Antonio Postigo, Ester Sánchez-Tilló, Andrew C.G. Porter, Simon D. Wagner. ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus. Biochemical Journal, 2010, 427 (3), pp.541-550. ⟨10.1042/BJ20091578⟩. ⟨hal-00479270⟩

Collections

PEER
128 Consultations
191 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More