Transcriptional silencing of RFXAP in MHC class II-deficiency

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 le...

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Bibliographic Details
Published in:Molecular immunology 2008-05, Vol.45 (10), p.2920-2928
Main Authors: van Eggermond, Marja C.J.A., Tezcan, Ilhan, Heemskerk, Mirjam H.M., van den Elsen, Peter J.
Format: Article
Language:English
Subjects:
5' Untranslated Regions - chemistry
5' Untranslated Regions - genetics
Bare lymphocyte syndrome
Base Pairing
Base Sequence
Blotting, Southern
Child, Preschool
Chromatin
Chromatin - metabolism
Female
Gene Silencing
HeLa Cells
Histocompatibility Antigens Class I - immunology
Homozygote
Humans
Lymphocyte Activation - immunology
MHC class II deficiency
Molecular Sequence Data
Mutagenesis, Insertional
Promoter
Promoter Regions, Genetic - genetics
RFXAP
RNA Polymerase II - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Analysis, DNA
Severe Combined Immunodeficiency - genetics
Transcription Factors - genetics
Transcription, Genetic
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Description
Summary: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.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2008.01.026