A TERNARY COMPLEX FACTOR-DEPENDENT MECHANISM MEDIATES INDUCTION OF EGR-1 THROUGH SELECTIVE SERUM RESPONSE ELEMENTS FOLLOWING ANTIGEN RECEPTOR CROSS-LINKING IN B-LYMPHOCYTES

Induction of the primary response gene egr-1 occurs rapidly following antigen receptor cross-linking in B lymphocytes. Antisense studies hav e demonstrated that this induction is necessary for their subsequent a ctivation to this signal. The present study examines the molecular mec hanism whereby the receptor-generated signals interact with the egr-1 promoter to elicit transcription. Deletion mapping and point mutations have indicated that two of the five serum response elements (SREs) in the egr-1 promoter can mediate induction. Of the two critical SREs, b oth are capable of mediating maximal induction even in the absence of the other SRE. Our results also indicate that adjacent Ets motifs are necessary for induction. Like the c-fos SRE, the egr-1 SRE/Ets sites a re occupied by a multiprotein (ternary) complex containing a homodimer of serum response factor and an unidentified member of the Ets family of transcription factors. The identification of a ternary complex-dep endent mechanism of egp-1 induction, along with selective utilization of SREs in B lymphocytes, suggests that a complicated array of signali ng cascades interacts with unique combinations of regulatory elements in the egr-1 promoter in different cell types.