title: Transcriptional silencing of RFXAP in MHC class II-deficiency.
abstract: 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 75bp 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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: Ilhan
authors.initials: I
authors.lastname: Tezcan
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D020029:Base Pairing; D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D002843:Chromatin / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006720:Homozygote; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D002843:Chromatin; D015395:Histocompatibility Antigens Class I; C413004:RFXAP protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D012319:RNA Polymerase II