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.
Rodríguez-Henche
Nieves
N
CNRS-UPR 9023, 141 rue de la Cardonille, 34094 Montpellier cedex 5, France.
Jamen
Françoise
F
Leroy
Céline
C
Bockaert
Joël
J
Brabet
Philippe
P
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D015698:Genomic Library; D008156:Luciferases / Q000235:genetics; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
C495504:Adcyap1r1 protein, mouse; D018797:Cell Cycle Proteins; C498423:Plagl1 protein, mouse; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases