E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivator promoter III (CIITA-PIII).
In B cells, expression of CIITA and resulting major histocompatibility complex II (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells, and monocytes. In this study we characterized the various regulatory elements and interacting factors of CIITA-PIII that account for specific activation in B lymphocytes. We identified 2 E-box motifs and an Ets/ISRE-consensus element (EICE) in CIITA-PIII as playing a crucial role in the B-cell-specific transcriptional regulation of CIITA. Abolishment of factor binding to these elements resulted in a strong reduction of CIITA-PIII activation in B cells only, whereas it did scarcely affect or not affect the activity of CIITA-PIII in activated T cells and monocytes. We show that in B cells, E47 and PU.1/IRF-4 interact with the E-box motifs and the EICE, respectively, and act synergistically in the activation of CIITA-PIII. Moreover, functional inhibition of either E47 or IRF-4 resulted in strong reduction of CIITA-PIII activity in B lymphocytes only. The finding that PU.1, IRF-4, and E47 play an important role in the B-cell-mediated activation of CIITA-PIII provides a link between antigen presentation functions and activation and differentiation events in B lymphocytes.
van der Stoep
Nienke
N
Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, E3-Q, PO Box 9600, 2300 RC Leiden, the Netherlands. nvdstoep@lumc.nl
Quinten
Edwin
E
Marcondes Rezende
Marisa
M
van den Elsen
Peter J
PJ
D001402:B-Lymphocytes / Q000378:metabolism*; D001665:Binding Sites; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology; D024721:E-Box Elements; D005809:Genes, Regulator; D006367:HeLa Cells; D006801:Humans; D050835:Interferon Regulatory Factors; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C083728:MHC class II transactivator protein; C544912:TCF7L1 protein, human