BASIC HELIX-LOOP-HELIX PROTEINS IN MURINE TYPE-C RETROVIRUS TRANSCRIPTIONAL REGULATION

E boxes, recognition sequences for basic helix-loop-helix (bHLH) trans cription factors, are detected in the enhancer and promoter regions of several murine type C retroviruses. Here we show that ALF1, a member of bHLH protein family of transcription factors, in vitro binds with d iffering affinities to distinct E-box sequences found in the U3 regula tory regions of Friend, Moloney, SL3-3, and Akv murine leukemia viruse s (MLVs) as well as Friend spleen focus-forming virus (SFFV). In NIH 3 T3 fibroblasts, ALF1 overexpression elevated transcription from the U3 region of Moloney MLV and the complete long terminal repeat regions o f Friend SFFV, Akv MLV, and SL3-3 MLV but neither from the U3 region n or from the complete long terminal repeat of Friend MLV. Introduction of mutations in the Akv MLV E boxes showed the E-box cis elements to b e required for the function of ALF1 as a transcription factor. ALF1 an d the glucocorticoid receptor, with overlapping DNA binding sequences, did not act synergistically with respect to transcriptional trans act ivation of expression from the Akv MLV promoter-enhancer region. We co nclude that ALF1 in vivo may be an important transcription regulator f or Akv, SL3-3, and Moloney MLVs as well as for Friend SFFV.