Transcription factor Tfec contributes to the IL-4-inducible expression of a small group of genes in mouse macrophages including the granulocyte colony-stimulating factor receptor.
Expression of the mouse transcription factor EC (Tfec) is restricted to the myeloid compartment, suggesting a function for Tfec in the development or function of these cells. However, mice lacking Tfec develop normally, indicating a redundant role for Tfec in myeloid cell development. We now report that Tfec is specifically induced in bone marrow-derived macrophages upon stimulation with the Th2 cytokines, IL-4 and IL-13, or LPS. LPS induced a rapid and transient up-regulation of Tfec mRNA expression and promoter activity, which was dependent on a functional NF-kappaB site. IL-4, however, induced a rapid, but long-lasting, increase in Tfec mRNA, which, in contrast to LPS stimulation, also resulted in detectable levels of Tfec protein. IL-4-induced transcription of Tfec was absent in macrophages lacking Stat6, and its promoter depended on two functional Stat6-binding sites. A global comparison of IL-4-induced genes in both wild-type and Tfec mutant macrophages revealed a surprisingly mild phenotype with only a few genes affected by Tfec deficiency. These included the G-CSFR (Csf3r) gene that was strongly up-regulated by IL-4 in wild-type macrophages and, to a lesser extent, in Tfec mutant macrophages. Our study also provides a general definition of the transcriptome in alternatively activated mouse macrophages and identifies a large number of novel genes characterizing this cell type.
Rehli
Michael
M
Department of Hematology and Oncology, University of Regensburg, Germany. michael.rehli@klinik.uni-regensburg.de
Sulzbacher
Sabine
S
Pape
Sabine
S
Ravasi
Timothy
T
Wells
Christine A
CA
Heinz
Sven
S
Söllner
Liane
L
El Chartouni
Carol
C
Krause
Stefan W
SW
Steingrimsson
Eirikur
E
Hume
David A
DA
Andreesen
Reinhard
R
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D008070:Lipopolysaccharides; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C484069:Tcfec protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4