PIP, A LYMPHOID-RESTRICTED IRF, CONTAINS REGULATORY DOMAIN THAT IS IMPORTANT FOR AUTOINHIBITION AND TERNARY COMPLEX-FORMATION WITH THE ETS FACTOR PU.1

Pip is a lymphoid-restricted IRF transcription factor that is recruite d to composite elements within immunoglobulin light-chain gene enhance rs through a specific interaction with the Ets factor PU.1. We have ex amined the transcriptional regulatory properties of Pip as well as the requirements for its interaction with PU.1 and DNA to form a ternary complex. We demonstrate that Pip is a dichotomous regulator; it specif ically stimulates transcription in conjunction with PU.1, but represse s alpha/beta-interferon-inducible transcription in the absence of PU.1 . Thus, during B-cell activation and differentiation, Pip may function both as an activator to promote B cell-specific gene expression and a s a repressor to inhibit the antiproliferative effects of alpha/beta-i nterferons. Mutational analysis of Pip reveals a carboxy-terminal segm ent that is important for autoinhibition of DNA binding and ternary co mplex formation. A domain of Pip containing this segment confers autoi nhibition and PU.1-dependent binding activity to the DNA-binding domai n of the related IRF family member, p48. On the basis of these and oth er data we propose a model for PU.1/Pip ternary complex formation.