A complex interplay of positive and negative elements is responsible for the different transcriptional activity of liver NF1 variants

Abstract

A full-length cDNA of the rat liver Nuclear Factor 1 (NF1L21) has been cloned and expressed in S. cerevisiae to analyse the architecture of its activation domain. NF1L21 displays a specific DNA-binding activity, as well as the ability to activate transcription from an artificial NF1-responsive promoter in yeast. Interaction of two or more NF1L21 molecules with multiple sites on the same promoter activated transcription in a synergistic fashion. Functional analysis of the activation domain of NF1L21 reveals a tripartite structure. Two distinct positive elements are required for NF1L21-mediated transcription activation. A proline-rich element sandwiched between these two positive domains attenuates their transactivation potential. A shorter NF1L variant (NF1L4) in which the distal positive element is replaced by a different sequence was also isolated. NF1L4 displays the same DNA-binding activity and dimerisation properties as NF1L21, but is unable to activate transcription in yeast. © 1995 Kluwer Academic Publishers.