ISSN:
0730-2312
Keywords:
negative regulatory element
;
heterologous promoter
;
DNA binding factor
;
transcriptional repression
;
milk protein expression control
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Expression of the whey acidic protein (WAP) gene is tightly regulated in a tissue and developmental stage specific manner, in that the WAP gene is exclusively expressed in the mammary gland during pregnancy and lactation. Using both deletion and competition analyses, evidence is provided for the existence of a negative regulatory element (NRE) in the WAP promoter loaated between 413 and 93 with respect to the WAP transcriptional initiation site. This NRE dramatically decreases transcription from linked heterologous promoter-reporter gene constructs. The activity of NRE requires WAP promoter sequences that are 230 bp apart since subfragments of the NRE fail to inhibit transcription of adjoining reporter genes. Nuclear extracts from different cell types, in whiah the WAP gene is not active, contain a protein or complex that specifically interacts with the entire NRE but not with subfragments of it. The contact points between this protein (NRE binding factor [NBF]) and element have been partially determined. Mutation of the implicated nucleotides severely peduces the ability of NBF to bind, and such promotep fragments dail to alleviate transcpiptional repression in competition experiments. This suggests that NBF binding to the NRE is at least il part responsible for the negative regulation of the WAP promoter. Since NBF is not detectable in the lactating mammary gland, where the WAP gene is expressed, we speculate that it may be a determinant of the expression spectrum of the WAP gene.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240560219
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