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Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis.


ABSTRACT: The gain-of-function mucin 5B (MUC5B) promoter variant, rs35705950, confers the largest risk, genetic or otherwise, for the development of idiopathic pulmonary fibrosis; however, the mechanisms underlying the regulation of MUC5B expression have yet to be elucidated. Here, we identify a critical regulatory domain that contains the MUC5B promoter variant and has a highly conserved forkhead box protein A2 (FOXA2) binding motif. This region is differentially methylated in association with idiopathic pulmonary fibrosis, MUC5B expression, and rs35705950. In addition, we show that this locus binds FOXA2 dynamically, and that binding of FOXA2 is necessary for enhanced expression of MUC5B. In aggregate, our findings identify novel targets to regulate the expression of MUC5B.

SUBMITTER: Helling BA 

PROVIDER: S-EPMC5516283 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis.

Helling Britney A BA   Gerber Anthony N AN   Kadiyala Vineela V   Sasse Sarah K SK   Pedersen Brent S BS   Sparks Lenore L   Nakano Yasushi Y   Okamoto Tsukasa T   Evans Christopher M CM   Yang Ivana V IV   Schwartz David A DA  

American journal of respiratory cell and molecular biology 20170701 1


The gain-of-function mucin 5B (MUC5B) promoter variant, rs35705950, confers the largest risk, genetic or otherwise, for the development of idiopathic pulmonary fibrosis; however, the mechanisms underlying the regulation of MUC5B expression have yet to be elucidated. Here, we identify a critical regulatory domain that contains the MUC5B promoter variant and has a highly conserved forkhead box protein A2 (FOXA2) binding motif. This region is differentially methylated in association with idiopathic  ...[more]

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