Transcription of the mouse PAC1 receptor gene: cell-specific expression and regulation by Zac1.

Regulations of the PACAP type 1 (PAC1) receptor expression have been described in the brain and the anterior pituitary. To understand the molecular mechanisms underlying mouse PAC1 gene regulation, we first mapped its transcription start sites (tss). PAC1 receptor RNA initiates from two major sites in embryos and adult tissues. Functional analysis revealed a basal promoter within the first 180 bp upstream of transcription start. Negative regulatory sequences upstream of this minimal promoter control the cell type-specific transcription of a luciferase reporter gene. Zac1, a zinc finger protein mainly expressed in the brain and the pituitary gland, binds to a GC-rich motif of the promoter regulatory elements. The Zac1 DNA binding site is required to positive and negative regulations of the promoter. Our findings provide bases for future studies on the regulatory elements controlling PAC1 gene transcription and demonstrate the PAC1 receptor promoter as a target of Zac1.