New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study
| Autor: | Emmanuèle Barras, Walter Reith, Madeleine Zufferey, Michal Krawczyk, Krzysztof Masternak |
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| Rok vydání: | 2005 |
| Předmět: |
RFXANK
Models Molecular Transcription Genetic Protein Conformation RNA Messenger/metabolism Gene Expression Cell Separation ddc:616.07 Protein Structure Secondary Transcription Factors/ genetics/metabolism/ physiology Promoter Regions Genetic Glutathione Transferase Genetics Nuclear Proteins Recombinant Fusion Proteins/chemistry Flow Cytometry Chromatin Cell biology DNA-Binding Proteins Glutathione Transferase/metabolism Plasmids Protein Binding Chromatin Immunoprecipitation Recombinant Fusion Proteins Molecular Sequence Data Nuclear Proteins/chemistry chemical and pharmacologic phenomena Biology Enhanceosome Cell Line Chromatin/metabolism Coactivator CIITA Humans Immunoprecipitation Amino Acid Sequence RNA Messenger Trans-Activators/chemistry Molecular Biology Transcription factor Sequence Homology Amino Acid Histocompatibility Antigens Class II Promoter Cell Biology Plasmids/metabolism Protein Structure Tertiary Mutagenesis Protein Biosynthesis Mutation Trans-Activators Ankyrin repeat RFX5 Transcription Factors |
| Zdroj: | Molecular and Cellular Biology, Vol. 25, No 19 (2005) pp. 8607-8618 |
| ISSN: | 0270-7306 |
| Popis: | The transcription factors RFX and CIITA are major players in regulation of the expression of all classical and nonclassical major histocompatibility complex class II (MHC-II) genes. RFX nucleates the formation of a multiprotein complex, called the MHC-II enhanceosome, on MHC-II promoters. Assembly of this enhanceosome is an obligatory step for recruitment of the coactivator CIITA and thus for activation of MHC-II gene transcription. We have analyzed the function of the ankyrin repeat-containing protein RFXANK, which forms the heterotrimeric RFX complex together with RFX5 and RFXAP. We discovered that ANKRA2, the closest paralogue of RFXANK, can substitute for RFXANK in the activation of MHC-II genes and that this ability is mediated by its ankyrin repeat domain (ARD). This finding provided the basis for a high-resolution structure-function analysis of the ARD of RFXANK, which allowed us to map the RFX5 interaction domain and residues critical for assembly of the RFX complex. We also found that mutations in the fourth ankyrin repeat of RFXANK abolish assembly of the enhanceosome on MHC-II promoters in vivo but not in vitro, suggesting a new role of RFXANK in facilitating promoter occupation in the context of chromatin. |
| Databáze: | OpenAIRE |
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