TAF4B begleitet die Differenzierung von humanen Makrophagen und bindet nach inflammatorischer Stimulation zusammen mit NFkappaB an den Promotor von tumor necrosis factor alpha

The TATA box binding protein associated factors (TAFs) of the TFIID complex, exert numerous functions which are essential for regulation of the transcription initiation. Several TAFs interact with transcription enhancer bound activators. This is necessary for the assembling of the transcription complex and activation of transcription by RNA polymerase II of numerous genes. The tissue specific TAF4B is a paraloge of the ubiquitous expressed TAF4. TAF4B interacts in various cell types specificly with transcription activators, for example NFkappaB RelA and cRel. Because of this, the coactivator TAF4B is necessary for the transduction of the NFkappaB induced activation of transcription by RNA polymerase II. Until now, a function of TAF4B was shown only for T and B lymphocytes. Aim of this work was to show a role of TAF4B in maturation and function of macrophages, cells of the innate immune system. The results point to an inhibited translation of TAF4B in primary, human monocytes. With the onset of adherence, the TAF4B protein is expressed in macrophages. Furthermore nuclear TAF4B colocalizes partially with active RNA polymerase II in this stage of the macrophage development, which indicates a transcriptional function of TAF4B in macrophage differentiation. In mature macrophages, stimulation with bacterial lipopolysaccharides induces the enrichment of TAF4B in the nucleus. Furthermore this stimulation induces a specific binding of TAF4B on the promoter of tumor necrosis factor alpha, along with the transcription activators RelA and cRel. The stimulation of the macrophages with inflammatory cytokines like Interferon gamma or Interleukin 4, 10 and 13 induces also a distinct localization of the TAF4B protein in mature macrophages, which points to a regulation of TAF4B by these cytokines.