The immunoglobulin lambda light chain enhancer consists of three modules which synergize in activation of transcription

V(D)J rearrangement, high level expression and somatic hypermutation of ass embled Ig genes is tightly controlled by a number of regulatory sequence el ements located in the vicinity of the J-, (D)-, and C-gene segments. During B cell maturation these elements become accessible to binding of trans-act ing factors, reflecting the opening of the chromatin structure through an a s yet unidentified mechanism. The mapping of regions of an altered chromati n structure (DNase I hypersensitivity) therefore is a powerful approach in identifying regulatory sequence elements. We here show that the human Ig la mbda enhancer consists of three modules previously identified by us as DNas e I-hypersensitive sites HSS-1, -2, and -3. The three sequence elements syn ergize in transcriptional activation of a reporter gene and together consti tute a powerful tissue-specific enhancer which is a much stronger transcrip tional activator than the kappa enhancers alone or in combination. We furth er show that the accessibility of the kappa and lambda enhancer elements fo r DNase I in the chromatin of a pre-B cell line (207) correlates with the t ranscriptional enhancer activities of kappa and lambda enhancer constructs. This finding is in support of an ordered model for Ig light chain activati on (kappa before lambda).