An interleukin 4-induced DNase I hypersensitive site indicates opening of the gamma 1 switch region prior to switch recombination.

Interleukin 4 (IL4) directs class switch recombination to the gamma 1 switch region (s gamma 1) in mitogen-activated murine B lymphocytes. The finding that transcription of the unrearranged s gamma 1 and its 5' flanking region is induced by IL4 prior to switch recombination had argued for the idea that IL4 promotes s mu/s gamma 1 switch recombination by selectively inducing accessibility of the gamma 1 switch region for a general switch recombinase. Here further evidence for this model is provided by showing that within less than 6 h IL4 induces a DNase I hypersensitive (HS) site 5' adjacent to the s gamma 1 region in activated murine B cells. This change in chromatin structure most likely reflects the IL4-responsive binding of regulatory proteins within or in the vicinity of the HS site. The result provides a candidate sequence for an IL4-dependent enhancer/promoter of transcription of s gamma 1.