TRANSCRIPTIONAL ACTIVATION OF THE MOUSE PERIPHERIN GENE BY LEUKEMIA INHIBITORY FACTOR - INVOLVEMENT OF STAT PROTEINS

Peripherin is a neuron-specific intermediate filament protein whose ex pression is activated in vitro by the neuropoietic cytokines leukemia inhibitory factor (LIF) and interleukin-6. We have studied the mechani sms of transcriptional activation of the peripherin gene by LIF. In pa rticular, we have identified a 70-bp element [peripherin cytokine-resp onsive element (Pe-CyRE)] within the 5'-flanking sequences of the mous e peripherin gene (between -930 and -860) that enhances transcription in two neuroblastoma cell lines, NBFL and LA-N-2, in response to LIF t reatment. We have also shown by DNA mobility shift assays that treatme nt of cells by LIF induces the binding of protein complexes composed o f at least two members of the signal transducers and activators of tra nscription (STAT) factor family to a cis element (Pe-APRE2) within Pe- CyRE. Furthermore, the entire PeCyRE, as well as Pe-APRE2, conferred r esponsiveness onto a heterologous thymidine kinase promoter. However, the response amplitude of the heterologous promoter to LIF was lower t han that observed with the 5'-flanking sequences of the peripherin pro moter, suggesting that cooperative interactions with surrounding seque nces of the peripherin gene are required for a full transcriptional ac tivation.