Analysis of genes regulated by the transcription factor LUMAN identifies ApoA4 as a target gene in dendritic cells

• Published in: Molecular immunology 2012-02, Vol.50 (1-2), p.66-73
• Main Authors: Sanecka, Anna, Ansems, Marleen, van Hout-Kuijer, Maaike A., Looman, Maaike W.G., Prosser, Amy C., Welten, Suzanne, Gilissen, Christian, Sama, Iziah E., Huynen, Martijn A., Veltman, Joris A., Jansen, Bastiaan J.H., Eleveld-Trancikova, Dagmar, Adema, Gosse J.
• Format: Article
• Language: English
• Subjects: Animals; Antigen-presenting cells; Apolipoproteins A - genetics; Bone marrow; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Brefeldin A - pharmacology; Cell Line; Cells, Cultured; Cyclic AMP Response Element-Binding Protein - genetics; DC-STAMP protein; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; DNA microarrays; Endoplasmic reticulum; Female; Gene expression microarray; Gene Expression Profiling; Gene Expression Regulation; HEK293 Cells; Humans; Immune system; Immunological tolerance; Immunotherapy; Membrane proteins; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Oligonucleotide Array Sequence Analysis; Promoters; Protein Synthesis Inhibitors - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Self; Transcription factors; Transcription regulation
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2011.12.003

► Retroviral overexpression of the active form of LUMAN in D2SC/1 cell line. ► Analysis of differentially expressed genes using microarray. ► Identification and validation of ApoA4 gene as a target of LUMAN in dendritic cells. Dendritic cells (DCs) are professional antigen presenting cells of the immune system that play a crucial role in initiating immune responses and maintaining self tolerance. Better understanding of the molecular basis of DC immunobiology is required to improve DC-based immunotherapies. We previously described the interaction of transcription factor LUMAN (also known as CREB3 or LZIP) with the DC-specific transmembrane protein DC-STAMP in DCs. Target genes of LUMAN and its role in DCs are currently unknown. In this study we set out to identify genes regulated by LUMAN in DCs using microarray analysis. Expression of a constitutively active form of LUMAN in mouse DC cell line D2SC/1 identified Apolipoprotein A4 (ApoA4) as its target gene. Subsequent validation experiments, bioinformatics-based promoter analysis, and silencing studies confirmed that ApoA4 is a true target gene of LUMAN in bone marrow-derived DCs (BMDCs).