NFI/X proteins: a class of NFI family of transcription factors with positive and negative regulatory domains

Abstract

NFI is a family of transcription factors that binds discrete nucleotide sequence and regulates transcriptional activity of genes. Transactivation occurs through proline-rich sequences. Among the genes whose transcriptional activity is regulated are those expressed in a cell-type specific manner. This suggests the possible existence of NFI proteins with distinct properties. With the use of the polymerase chain reaction technique, we have cloned and analyzed the activity of three spliced variants of NFI (class X) genes in murine cells. Expression vectors containing the regulatory regions of these proteins fused to the DNA binding domain of the yeast transcription factor GAL4 helped identify both negative and positive regulatory domains. In the context of the whole NFI/X proteins, spliced variants lacking the positive regulatory sequences functioned as repressors, whereas those containing both regulatory domains functioned as weak activators. With the identification of the negative domain in the NFI/X proteins, we demonstrate here a novel regulatory feature of these proteins in positive and negative modulation of gene expression.