Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G

Hum Immunol. 2000 Nov;61(11):1102-7. doi: 10.1016/s0198-8859(00)00198-1.

Abstract

The restricted tissue expression of the MHC class Ib molecules HLA-E, HLA-F, and HLA-G has suggested specialized functions and tight transcriptional control of their genes. Transactivation of classical MHC class I genes is mediated by two groups of juxtaposed cis-acting elements, which can be viewed as regulatory modules. The most upstream module consists of the enhancer A and ISRE, and mediates constitutive and cytokine induced expression, whereas the SXY module is important for the constitutive and CIITA-mediated transactivation of MHC class I genes. Nucleotide sequence divergence in these regulatory elements in the promoters of HLA-E, HLA-F, or HLA-G determines their differential responsiveness to NF-kappaB, IRF1, and CIITA-mediated induction. HLA-E is not inducible by NF-kappaB or IRF1, but is responsive to IFN-gamma through an upstream STAT1 binding site. Furthermore, HLA-E is inducible by CIITA through the SXY regulatory module. HLA-F is inducible by NF-kappaB through the kappaB1 site of enhancer A, is responsive to IFN-gamma through the ISRE, and is inducible by CIITA. Both regulatory modules are divergent in HLA-G rendering this gene unresponsive to NF-kappaB, IRF1, and CIITA-mediated induction. This implies a unique regulation of HLA-G transcription amongst the MHC class Ib genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Base Sequence
  • Genes, MHC Class I*
  • HLA Antigens / genetics*
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Molecular Sequence Data
  • Regulatory Sequences, Nucleic Acid
  • Transcriptional Activation*
  • Trophoblasts / metabolism

Substances

  • HLA Antigens
  • HLA-E antigen
  • HLA-F antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I