Article scientifique

New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study

Publié dansMolecular and cellular biology, vol. 25, no. 19, p. 8607-8618
Date de publication2005

The transcription factors RFX and CIITA are major players in regulation of the expression of all classical and nonclassical major histocompatibility complex class II (MHC-II) genes. RFX nucleates the formation of a multiprotein complex, called the MHC-II enhanceosome, on MHC-II promoters. Assembly of this enhanceosome is an obligatory step for recruitment of the coactivator CIITA and thus for activation of MHC-II gene transcription. We have analyzed the function of the ankyrin repeat-containing protein RFXANK, which forms the heterotrimeric RFX complex together with RFX5 and RFXAP. We discovered that ANKRA2, the closest paralogue of RFXANK, can substitute for RFXANK in the activation of MHC-II genes and that this ability is mediated by its ankyrin repeat domain (ARD). This finding provided the basis for a high-resolution structure-function analysis of the ARD of RFXANK, which allowed us to map the RFX5 interaction domain and residues critical for assembly of the RFX complex. We also found that mutations in the fourth ankyrin repeat of RFXANK abolish assembly of the enhanceosome on MHC-II promoters in vivo but not in vitro, suggesting a new role of RFXANK in facilitating promoter occupation in the context of chromatin.

  • Amino Acid Sequence
  • Cell Line
  • Cell Separation
  • Chromatin/metabolism
  • Chromatin Immunoprecipitation
  • Flow Cytometry
  • Glutathione Transferase/metabolism
  • Histocompatibility Antigens Class II
  • Humans
  • Immunoprecipitation
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Nuclear Proteins/chemistry
  • Plasmids/metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Messenger/metabolism
  • Recombinant Fusion Proteins/chemistry
  • Sequence Homology, Amino Acid
  • Trans-Activators/chemistry
  • Transcription Factors/ genetics/metabolism/ physiology
  • Transcription, Genetic
Structure d'affiliation Pas une publication de l'UNIGE
Citation (format ISO)
KRAWCZYK, Michal et al. New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study. In: Molecular and cellular biology, 2005, vol. 25, n° 19, p. 8607–8618. doi: 10.1128/MCB.25.19.8607-8618.2005
Correctifs (1)
ISSN du journal0270-7306

Informations techniques

Création27/08/2010 13:35:13
Première validation27/08/2010 13:35:13
Heure de mise à jour14/03/2023 16:04:04
Changement de statut14/03/2023 16:04:04
Dernière indexation18/10/2023 11:22:14
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack