Transcriptional silencing of RFXAP in MHC class II-deficiency


van Eggermond M. C. J. A. , Tezcan I., Heemskerk M. H. M. , van den Eisen P. J.

MOLECULAR IMMUNOLOGY, cilt.45, ss.2920-2928, 2008 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 45 Konu: 10
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1016/j.molimm.2008.01.026
  • Dergi Adı: MOLECULAR IMMUNOLOGY
  • Sayfa Sayıları: ss.2920-2928

Özet

MHC-II deficiency is recognized by defects in components of the RFX complex or CIITA. In this study, we have characterized at the molecular level the putative defect in MHC-II regulatory factors of a recently identified MHC-II deficiency patient (FGK). We found that this patient lacked detectable levels of mRNA and protein of the RFX complex subunit RFXAP. It was subsequently established that the RFXAP gene in FGK differed from wild type RFXAP by a homozygous 75 bp insertion in the 5'-UTR, which impaired the activity of the FGK RFXAP promoter. The transcriptional silent state of RFXAP correlated with reduced recruitment of RNA polymerase II to FGK RFXAP chromatin. Together, this insertion in the promoter region represents a novel type of MHC-II gene silencing in MHC-II deficiency patients. (c) 2008 Elsevier Ltd. All rights reserved.