Neuron-specific transcriptional promoter

Details Neuron-specific transcriptional promoter Neuron-specific transcriptional promoter

1997-07-08

2000-05-23

Elliott, George C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 231, 536 245, 435353, 435368, 435375, C07H 2104, C12N 1511, C12N 1585

Patent

active

060667265

ABSTRACT:
The 5'-flanking region and core regulatory domains that underlie neuronal specific expression of the human .gamma.-aminobutyric acid type A (GABA.sub.A) receptor .beta.1 subunit gene are identified herein. Sequence analysis, mapping of transcriptional initiation sites, and transfection of reporter gene constructs into primary cultures demonstrate that neuronal and region specific activity resides in a TATA-less minimal promoter of 186 bp, comprising an initiator, the major transcriptional start site, a presumptive TFIID binding site, and an enhancer. Enhancer sequence contained within a 26 bp region at the 5'-end of the minimal promoter is essential for activity but not for tissue specificity. Moreover, .beta.1 promoter activity is subject to autologous inhibition, indicating that GABA-induced receptor mRNA downregulation results from an inhibition of gene transcription. Regulation of neurotransmitter receptor gene expression plays an important role in nervous system development and function, and impaired gene regulation may underlie the etiology of certain neurological diseases.

REFERENCES:
Kirkness et al., EMBL3, Accession No. M59212, Aug. 6, 1991.

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