A variation in a Pit-1 site in the growth hormone gene (GH1) promoter induces a differential transcriptional activity.
The proximal promoter of the human growth hormone gene (GH1) is highly polymorphic. We tested if promoter haplotypes differing at possibly functional sites, namely -278T/G (in the NF1 binding site), -75A/G (in the proximal Pit-1 binding site) and -57G/T (in the VDR binding site), induced a different luciferase activity when transfected in a rat pituitary cell line. The presence of a G instead of an A at position -75 induced a more than two-fold reduced activity (p<0.0001). In accordance with this findings the electrophoretic mobility shift assay demonstrated a reduced affinity of the -75G for the pituitary transcription factor Pit-1. Despite the strong effect of this polymorphism in vitro, the -75G variation was not associated to an impairment of the GH secretion in vivo.
Giordano
Mara
M
Laboratorio di Genetica Umana, Dipartimento di Scienze Mediche and IRCAD, Università del Piemonte Orientale, Novara, Italy. giordano@med.unipmn.it
Godi
Michela
M
Giacopelli
Francesca
F
Lessi
Monica
M
Mellone
Simona
S
Paracchini
Roberta
R
Petri
Antonella
A
Bellone
Jaele
J
Ravazzolo
Roberto
R
Bona
Gianni
G
Momigliano-Richiardi
Patricia
P
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006239:Haplotypes; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D051381:Rats; D050817:Transcription Factor Pit-1 / Q000378:metabolism*
D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone; D008156:Luciferases