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First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding.

Abstract：

:Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Taulan M,Lopez E,Guittard C,René C,Baux D,Altieri JP,DesGeorges M,Claustres M,Romey MC

doi

10.1016/j.bbrc.2007.07.091

subject

Has Abstract

pub_date

2007-09-28 00:00:00

pages

775-81

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)01580-X

journal_volume

361

pub_type

杂志文章

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