en
Scientific article
English

Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA

Published inThe Journal of immunology, vol. 173, no. 10, p. 6200-6210
Publication date2004
Abstract

MHC class II (MHC-II) genes are regulated by an enhanceosome complex containing two gene-specific transcription factors, regulatory factor X complex (RFX) and CIITA. These factors assemble on a strictly conserved regulatory module (S-X-X2-Y) found immediately upstream of the promoters of all classical and nonclassical MHC-II genes as well as the invariant chain (Ii) gene. To identify new targets of RFX and CIITA, we developed a computational approach based on the unique and highly constrained architecture of the composite S-Y motif. We identified six novel S'-Y' modules situated far away from the promoters of known human RFX- and CIITA-controlled genes. Four are situated at strategic positions within the MHC-II locus, and two are found within the Ii gene. These S'-Y' modules function as transcriptional enhancers, are bona fide targets of RFX and CIITA in B cells and IFN-gamma-induced cells, and induce broad domains of histone hyperacetylation. These results reveal a hitherto unexpected level of complexity involving long distance control of MHC-II expression by multiple distal regulatory elements.

Keywords
  • Acetylation
  • Acetyltransferases/metabolism
  • Antigens, Differentiation, B-Lymphocyte/genetics/metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Computational Biology/methods
  • Conserved Sequence
  • DNA-Binding Proteins/metabolism/ physiology
  • Enhancer Elements, Genetic/ physiology
  • Gene Expression Profiling/methods
  • Genes, MHC Class II
  • Genetic Markers/immunology
  • Histocompatibility Antigens Class II/genetics/metabolism
  • Histone Acetyltransferases
  • Histones/metabolism
  • Humans
  • Interferon-gamma/physiology
  • Locus Control Region/ physiology
  • Molecular Sequence Data
  • Nuclear Proteins/metabolism/ physiology
  • Promoter Regions, Genetic
  • Protein Binding/genetics/immunology
  • Trans-Activators/metabolism/ physiology
  • Transcription Factors/metabolism/ physiology
Affiliation Not a UNIGE publication
Citation (ISO format)
KRAWCZYK, Michal et al. Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA. In: The Journal of immunology, 2004, vol. 173, n° 10, p. 6200–6210. doi: 10.4049/jimmunol.173.10.6200
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0022-1767
569views
0downloads

Technical informations

Creation08/27/2010 1:35:13 PM
First validation08/27/2010 1:35:13 PM
Update time03/14/2023 4:04:04 PM
Status update03/14/2023 4:04:04 PM
Last indexation02/12/2024 7:19:54 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack