Transcriptional regulation of the human neuropeptide Y gene by nerve growth factor.

ABSTRACT

Neuropeptide Y (NPY) is the most ubiquitously expressed peptide in the mammalian nervous system. Transcription of the NPY gene in PC12 cells is regulated by a number of agents, including the neurotrophic peptide nerve growth factor (NGF). In this paper, we define the cis-acting promoter elements which respond to NGF and characterize the trans-acting factors which interact with these sequences. The NGF-responsive elements of the NPY gene lie between nucleotides -87 and -36. At least four proteins interact with this promoter region. One of these proteins interacts with a CT-rich sequence centered at position -51, which closely abuts a binding site for transcription factor AP-2 centered at position -63. Two newly characterized factors bind between positions -87 and -58. These proteins are expressed in a tissue-specific manner and, together with the other binding activities, modulate the transcriptional activity of the NPY gene. These results suggest that the concerted interplay of these proteins, in response to NGF, increases the transcriptional activity of the NPY gene.