Functional synergism of STAT6 with either NF-kappa B or PU.1 to mediate IL-4-induced activation of IgE germline gene transcription.

摘要: Ig heavy chain class switching to IgE is directed by IL-4 and IL-13 inducing transcription from the germline promoter. A crucial factor in this process STAT6, which binds a specific DNA element upon cytokine activation. In paper it shown that B cell- monocyte-specific PU.1 interacts with closely spaced sequence human promoter overlaps previously described binding site for NFκB/ rel . The authenticity of was demonstrated competition supershifts EMSA experiments. addition, vitro translated could interact an oligonucleotide derived containing migrated same mobility compared complex formed nuclear extracts. Transient transfection experiments using reporter gene constructs mutations affecting or had no little effect on inducibility these plasmids. However, point abolished both factors abrogated inducibility. No strict spacing STAT6 composite PU.1/NF-κB elements required induction. IL-4-induced retained − /NFκB/ double mutants. data demonstrate cooperation at least necessary activation transcription.