Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development.

ABSTRACT:

Background

Diverse molecular alterations associated with smoking in normal and precursor lung cancer cells have been reported, yet their role in lung cancer etiology remains unclear. A prominent example is hypomethylation of the aryl hydrocarbon-receptor repressor (AHRR) locus, which is observed in blood and squamous epithelial cells of smokers, but not in lung cancer.

Results

Using a novel systems-epigenomics algorithm, called SEPIRA, which leverages the power of a large RNA-sequencing expression compendium to infer regulatory activity from messenger RNA expression or DNA methylation (DNAm) profiles, we infer the landscape of binding activity of lung-specific transcription factors (TFs) in lung carcinogenesis. We show that lung-specific TFs become preferentially inactivated

SUBMITTER: Chen Y 

PROVIDER: S-EPMC5738803 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature