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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| Veröffentlicht in: | Molecular immunology 2008-05, Vol.45 (10), p.2920-2928 |
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| container_title | Molecular immunology |
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| creator | van Eggermond, Marja C.J.A. Tezcan, Ilhan Heemskerk, Mirjam H.M. van den Elsen, Peter J. |
| description | 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. |
| doi_str_mv | 10.1016/j.molimm.2008.01.026 |
| format | Article |
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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.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/j.molimm.2008.01.026</identifier><identifier>PMID: 18336911</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>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</subject><ispartof>Molecular immunology, 2008-05, Vol.45 (10), p.2920-2928</ispartof><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-e241616ba3aa50e919c22156d9e62b73ce2cac9228afa66eab46165e7c473bc73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molimm.2008.01.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18336911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Eggermond, Marja C.J.A.</creatorcontrib><creatorcontrib>Tezcan, Ilhan</creatorcontrib><creatorcontrib>Heemskerk, Mirjam H.M.</creatorcontrib><creatorcontrib>van den Elsen, Peter J.</creatorcontrib><title>Transcriptional silencing of RFXAP in MHC class II-deficiency</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>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.</description><subject>5' Untranslated Regions - chemistry</subject><subject>5' Untranslated Regions - genetics</subject><subject>Bare lymphocyte syndrome</subject><subject>Base Pairing</subject><subject>Base Sequence</subject><subject>Blotting, Southern</subject><subject>Child, Preschool</subject><subject>Chromatin</subject><subject>Chromatin - metabolism</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>HeLa Cells</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Lymphocyte Activation - immunology</subject><subject>MHC class II deficiency</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Insertional</subject><subject>Promoter</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>RFXAP</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Severe Combined Immunodeficiency - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Transcription, Genetic</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90E1LwzAYwPEgipvTbyDSk55a89KmyUFhDOcGE0UmeAtp-lQy-jKTTti3N3MDbzvl8nueJH-ErglOCCb8fpU0XW2bJqEYiwSTBFN-goZE5DSWJKWnaBgYiTMh8QBdeL_CGHPMs3M0IIIxLgkZooel0603zq5727W6jrytoTW2_Yq6Knqffo7fIttGL7NJZGrtfTSfxyVU1tigtpforNK1h6vDOUIf06flZBYvXp_nk_EiNillfQw0DS_hhWZaZxgkkYZSkvFSAqdFzgxQo42kVOhKcw66SAPPIDdpzgqTsxG62-9du-57A75XjfUG6lq30G28EoKFv3KRBnl7VBKZhzZ8B9M9NK7z3kGl1s422m0VwWoXWK3UPrDaBVaYqBA4jN0c9m-KBsr_oUPRAB73AEKPHwtO-b9WUFoHpldlZ4_f8Au2VIxM</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>van Eggermond, Marja C.J.A.</creator><creator>Tezcan, Ilhan</creator><creator>Heemskerk, Mirjam H.M.</creator><creator>van den Elsen, Peter J.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope></search><sort><creationdate>20080501</creationdate><title>Transcriptional silencing of RFXAP in MHC class II-deficiency</title><author>van Eggermond, Marja C.J.A. ; Tezcan, Ilhan ; Heemskerk, Mirjam H.M. ; van den Elsen, Peter J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-e241616ba3aa50e919c22156d9e62b73ce2cac9228afa66eab46165e7c473bc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>5' Untranslated Regions - chemistry</topic><topic>5' Untranslated Regions - genetics</topic><topic>Bare lymphocyte syndrome</topic><topic>Base Pairing</topic><topic>Base Sequence</topic><topic>Blotting, Southern</topic><topic>Child, Preschool</topic><topic>Chromatin</topic><topic>Chromatin - metabolism</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>HeLa Cells</topic><topic>Histocompatibility Antigens Class I - immunology</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Lymphocyte Activation - immunology</topic><topic>MHC class II deficiency</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Insertional</topic><topic>Promoter</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>RFXAP</topic><topic>RNA Polymerase II - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>Severe Combined Immunodeficiency - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Eggermond, Marja C.J.A.</creatorcontrib><creatorcontrib>Tezcan, Ilhan</creatorcontrib><creatorcontrib>Heemskerk, Mirjam H.M.</creatorcontrib><creatorcontrib>van den Elsen, Peter J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Eggermond, Marja C.J.A.</au><au>Tezcan, Ilhan</au><au>Heemskerk, Mirjam H.M.</au><au>van den Elsen, Peter J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional silencing of RFXAP in MHC class II-deficiency</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>45</volume><issue>10</issue><spage>2920</spage><epage>2928</epage><pages>2920-2928</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><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 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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>18336911</pmid><doi>10.1016/j.molimm.2008.01.026</doi><tpages>9</tpages></addata></record> |
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| ispartof | Molecular immunology, 2008-05, Vol.45 (10), p.2920-2928 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| 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 |
| title | Transcriptional silencing of RFXAP in MHC class II-deficiency |
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