A COMPLEX INTERPLAY OF POSITIVE AND NEGATIVE ELEMENTS IS RESPONSIBLE FOR THE DIFFERENT TRANSCRIPTIONAL ACTIVITY OF LIVER NF1 VARIANTS

A full-length cDNA of the rat liver Nuclear Factor 1 (NF1L(21)) has be en cloned and expressed in S. cerevisiae to analyse the architecture o f its activation domain. NF1L(21) displays a specific DNA-binding acti vity, as well as the ability to activate transcription from an artific ial NE1-responsive promoter in yeast. Interaction of two or more NF1L( 21) molecules with multiple sites on the same promoter activated trans cription in a synergistic fashion. Functional analysis of the activati on domain of NF1L(21) reveals a tripartite structure. Two distinct pos itive elements are required for NF1L(21)-mediated transcription activa tion. A proline-rich element sandwiched between these two positive dom ains attenuates their transactivation potential. A shorter NF1L varian t (NFIL(4)) in which the distal positive element is replaced by a diff erent sequence was also isolated. NF1L(4) displays the same DNA-bindin g activity and dimerisation properties as NF1L(21), but is unable to a ctivate transcription in yeast.