PU-1 IS A COMPONENT OF A MULTIPROTEIN COMPLEX WHICH BINDS AN ESSENTIAL SITE IN THE MURINE IMMUNOGLOBULIN LAMBDA-2-4 ENHANCER

B-cell-specific enhancers have been identified in the immunoglobulin lambda locus 3' of each constant-region cluster. These enhancers contain two distinct domains, lambdaA and lambdaB, which are essential for enhancer function. lambdaB contains a near-consensus binding site for the Ets family of transcription factors. In this study, we have identified a B-cell-specific protein complex which binds the lambdaB motif of the lambda2-4 enhancer in vitro and appears necessary for the activity of the enhancer in vivo, since mutations in lambdaB which prevent this interaction also eliminate enhancer function. This complex contains PU.1, a member of the Ets family, and a transcriptional activator whose expression is restricted to cells of the hematopoietic system with the exception of T lymphocytes. In addition, it contains a factor which binds specifically to a region adjacent to the PU.1 binding site. This factor cannot bind lambdaB autonomously but appears to require interaction with the PU.1 protein to stabilize its association with the DNA. This complex may be identical or related to the PU.1/NF-EM5 complex which interacts with a homologous DNA element in the immunoglobulin kappa 3' enhancer.