A MUC5B polymorphism associated with Idiopathic Pulmonary Fibrosis mediates overexpression through decreased CpG methylation and C/EBPb transcriptional activation
Armesto-Jimenez, A. U.; Arason, A. J.; Stefasson, O. A.; Gudmundsson, G.; Gudjonsson, T.; Magnusson, M. K.
Show abstract
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/EBP{beta} 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/EBP{beta} as an important regulatory factor in the development of IPF.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression. 94%
- Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 93%
- Identification of a distal RXFP1 gene enhancer with differential activity in fibrotic lung fibroblasts involving AP-1 93%
Similar papers in this journal
Similar papers in this journal
- Germline ERBB3 mutation in familial non-small cell lung carcinoma: expanding the role of the ErbB family in oncogenesis. 92%
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT 91%
- The role of alternative polyadenylation in Epithelial-mesenchymal transition of non-small cell lung cancer 90%
Similar papers in this journal
- A single cysteine residue in vimentin regulates long non-coding RNA XIST to suppress epithelial-mesenchymal transition and stemness in breast cancer 92%
- Reversing chemorefraction in colorectal cancer cells by controlling mucin secretion 92%
- CD8+ tissue-resident memory T cells triggered the erosion of oral lichen planus by the cytokine network 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.