A Functionally Essential Domain of RFX5 Mediates Activation of Major Histocompatibility Complex Class II Promoters by Promoting Cooperative Binding between RFX and NF-Y

Villard, Jean; Peretti, Marie; Masternak, Krzysztof; Barras, Emmanuèle; Caretti, Giuseppina; Mantovani, Roberto; Reith, Walter

doi:10.1128/mcb.20.10.3364-3376.2000

Cited by 68 publications

(55 citation statements)

References 82 publications

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“…In addition, RFX5 is essential for activation of MHC-II promoters (87). An increase in the expression of these genes, whose protein products are instrumental in processing and presentation of viral antigens by infected cells, is not surprising.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the host transcriptional response to human cytomegalovirus infection

Challacombe

Rechtsteiner

Gottardo

et al. 2004

Physiological Genomics

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Gene expression data from human cytomegalovirus (HCMV)-infected cells were analyzed using DNA-Chip Analyzer (dChip) followed by singular value decomposition (SVD) and compared with a previous analysis of the same data that employed GeneChip software and a fold change filtering approach. dChip and SVD analysis revealed two clusters of coexpressed human genes responding differently to HCMV infection: one containing some genes identified previously, and another that was largely unique to this analysis. Annotating these genes, we identified several functional categories important to host cell responses to HCMV infection. These categories included genes involved in transcriptional regulation, oncogenesis, and cell cycle regulation, which were more prevalent in cluster 1, and genes involved in immune system regulation, signal transduction, and cell adhesion, which were more prevalent in cluster 2. Within these categories, we found genes involved in the host response to HCMV infection (mainly in cluster 1), as well as genes targeted by HCMV’s immune evasion strategies (mainly in cluster 2). As the second group of genes identified by the dChip and SVD approach was statistically and biologically significant, our results point out the advantages of using different methods to analyze gene expression data.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the host transcriptional response to human cytomegalovirus infection

Challacombe

Rechtsteiner

Gottardo

et al. 2004

Physiological Genomics

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“…We have found by EMSA that an inducible protein binds specifically to this site. In supershift experiments using a specific Ab, we excluded that this protein is RFX5, one of several proteins that were shown to bind X boxes in promoters of MHC class II genes (25). The Ϫ45/Ϫ41 site is identical with a consensus E box and may serve as a binding site for the USF (32).…”

Section: Discussionmentioning

confidence: 99%

“…Mutation of nucleotides Ϫ45/Ϫ41 inhibited the formation of band 1, but not band 2, indicating that the protein present in band 1 may be functionally relevant. Addition of an Ab specific for RFX5, which was shown to bind X-boxes in promoters of MHC class II genes (25), had no effect on the intensity of the bands. Finally, Abs against Jun/AP-1 or CREB did not alter the appearance of the bands.…”

Section: Identification Of Transcription Factors That Bind To Functiomentioning

confidence: 99%

Multiple Transcription Factors Regulate the Inducible Expression of the Human Complement Receptor 2 Promoter

Vereshchagina

Tolnay

Tsokos

2001

The Journal of Immunology

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Complement receptor 2 (CR2) is regulated at the transcriptional level, but the promoter elements and the transcription factors that bind to them and contribute to its regulation are unknown. After documenting that PMA and cAMP induced the activity of the CR2 promoter by 10-fold, we conducted promoter truncation and mutagenesis experiments, in conjunction with shift assays, to determine the functionally important regions of the promoter and the proteins that bind to them. We identified two regions, separated by ∼900 nucleotides, which together were responsible for inducible promoter activity. Mutagenesis of single promoter elements demonstrated a functional upstream stimulatory factor/E box in the TATA box-proximal region and three equally important, closely spaced, CREB/AP-1 half-sites in the upstream promoter region. The cAMP response element-binding protein (CREB)/AP-1 half-sites bound in vitro Jun and CREB that are induced by protein kinases A and/or C. The 900-nucleotide segment stretching between the above two regions had no functional impact on the induced transcription, and its deletion increased the promoter activity. Finally, a region upstream of the distal site had a repressor activity on CR2 transcription. Moreover, IL-4 induced binding of CREB and AP-1 to the upstream promoter elements and resulted in increased CR2 surface protein expression. These studies have characterized regions of the CR2 promoter and the transcription factors that bind to them and are crucial to induced CR2 expression. Our studies may provide insights to novel approaches to modulate B cell function by regulating CR2 gene transcription.

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“…Several publications demonstrate that the RFX, NFY, and X2BP complexes bind cooperatively to MHC class II promoters, and that their interaction increases the stability of the complexes to the promoters (20,21). More recently, RFX5 was shown to create a bridge in between NFY, RFXAP, and RFXANK (22). Functional complementation of group A mutants has led to the identification of the CIITA gene (class II transactivator) (23).…”

Section: T He Mhc Class II Molecules (Hla-dr Hla-dp and Hla-dq) Prementioning

confidence: 99%

Uncoordinated HLA-D Gene Expression in a RFXANK-Defective Patient with MHC Class II Deficiency

Lennon-Duménil

Barbouche

Vedrenne

et al. 2001

The Journal of Immunology

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We describe the analysis of a patient, JER, presenting classical immunological features of MHC class II deficiency. Unexpectedly, some HLA transcripts (HLA-DRA, HLA-DQA, and HLA-DMA) were found to be expressed in the JER cell line at nearly wild-type levels, while HLA-DPA and the HLA-D β-chain transcripts were not detected. Gene reporter experiments confirmed the differential transcriptional activities driven by the HLA-D promoters in the JER cells. A defect in RFXANK was first suggested by genetic complementation analyses, then assessed with the demonstration of a homozygous mutation affecting a splice donor site downstream exon 4 of RFXANK. Because the severe deletion of the resulting protein cannot account for the expression of certain HLA-D genes, minor alternative transcripts of the RFXANK gene were analyzed. We thereby showed the existence of a transcript lacking exon 4, encoding a 28-aa-deleted protein that retains a transcriptional activity. Altogether, we characterize a new type of mutation in the RFXANK gene in a MHC class II-defective patient leading to an uncoordinated expression of the HLA-D genes, and propose that this phenotype is ensured by severely limited amounts of an active, although truncated RFXANK protein.

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A Functionally Essential Domain of RFX5 Mediates Activation of Major Histocompatibility Complex Class II Promoters by Promoting Cooperative Binding between RFX and NF-Y

Abstract: Major histocompatibility complex class II (MHC-II

Cited by 68 publications

References 82 publications

Evaluation of the host transcriptional response to human cytomegalovirus infection

Evaluation of the host transcriptional response to human cytomegalovirus infection

Multiple Transcription Factors Regulate the Inducible Expression of the Human Complement Receptor 2 Promoter

Uncoordinated HLA-D Gene Expression in a RFXANK-Defective Patient with MHC Class II Deficiency

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