Transcriptional Regulation of the Neurofibromatosis Type 1 Gene

Abstract : The goal of this project was to understand the transcriptional regulation of the NFl gene. Specifically to further characterize TLF-mediated regulation and identify new factors that participate in the control of NFl regulation. In addition, an attempt was made to determine signaling pathways that affect NFl levels. We found that TLF(TRF2) activates a number of different genes that include the Neurofibromatosis I (NFl)gene. Overexpression of TLF increases the amount of NFl mRNA in cells. In vivo, TLF binds and up regulates transcription from a fragment of the NFl promoter. In vitro, purified TLF-TFIIA binds directly to the same NFl promoter fragment that is required for TLF-responsiveness in cells. In contrast, TLF inhibits transcription driven by a fragment of the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NFl and c-fos promoters in a reciprocal manner to TLF, stimulating the c-fos promoter and inhibiting NFl transcription. Thus, it appears that TLF is a functional regulator of transcription with targets distinct from those of TBP.