Functional domains in the oxytocin gene for regulation of expression and biosynthesis of gene products.
In the oxytocin (OT) gene several regions can be discerned that have a function in regulating its expression. Firstly, in the proximal 5' flanking region regulatory elements have been discovered that are targets for transcription factors of the nuclear hormone receptor family. Through these elements the OT gene of rat and man is responsive to estrogens, thyroid hormones and retinoids. Furthermore, these elements can be employed by the nuclear hormone orphan receptor family for repressive or inductive actions. In the distal 5' flanking region the POU class III proteins Brn-1, Brn-2, Brn-4, that are expressed in magnocellular neurons, and Oct-6 are able to bind, but do not display a significant regulatory activity on the OT gene in heterologous expression systems. Secondly, the OT precursor harbours both the biologically active hormone and the protein neurophysin that is able to associate with the hormone. Heterologous expression of wild-type and mutant vasopressin cDNAs in peptidergic cell lines shows that the highly homologous vasopressin-associated neurophysin domain associates with the hormone domain within the prohormone. This intramolecular interaction between two prohormone domains serves an essential intracellular function, i.e. the proper sorting of the prohormone into the regulated secretory pathway.
Burbach
J P
JP
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht and University, The Netherlands.
van Schaick
H S
HS
de Bree
F M
FM
Lopes da Silva
S
S
Adan
R A
RA
D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006801:Humans; D009481:Neurophysins / Q000378:metabolism; D050816:Octamer Transcription Factor-6; D010121:Oxytocin / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D009481:Neurophysins; C494178:POU3F1 protein, human; C494179:Pou3f1 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001127:Arginine Vasopressin; D050816:Octamer Transcription Factor-6; D010121:Oxytocin