A MUC5B polymorphism associated with Idiopathic Pulmonary Fibrosis mediates overexpression through decreased CpG methylation and C/EBPb transcriptional activation
Idiopathic pulmonary fibrosis is a progressive and fatal lung disease of unknown aetiology. The strongest genetic risk factor associated with IPF development is a MUC5B promoter polymorphism (rs35705950). However, the mechanism underlying its effects remains unknown. In this study we have focused on the molecular consequences of the polymorphism on the regulation of MUC5B expression. We have identified a combined mechanism involving both methylation and direct transcriptional regulation mediated by the polymorphic variant on MUC5B overexpression. Our results demonstrate that the minor allele (T) associated with rs35705950 disturbs a DNA methylation site, directly increasing MUC5B expression. Furthermore, this same variant also creates a novel binding site for the transcription factor C/EBPβ leading to transcriptional activation of MUC5B. Our findings provide a novel insight into the regulatory effects of the IPF risk allele, rs35705950 and identifies C/EBPβ as an important regulatory factor in the development of IPF.
- Downloaded 302 times
- Download rankings, all-time:
- Site-wide: 87,764
- In genetics: 3,932
- Year to date:
- Site-wide: 81,768
- Since beginning of last month:
- Site-wide: 89,196
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!