Epigenetic dysregulation of IRF9 drives excessive interferon signalling in COPD

ABSTRACT: Altered respiratory barrier integrity and impaired lung regeneration are hallmarks of chronic obstructive pulmonary disease (COPD). To investigate the molecular mechanisms driving the impaired regeneration of alveolar epithelial progenitors in COPD, we generated whole-genome DNA methylation and transcriptome maps of sorted human primary alveolar type 2 cells (AT2) at different disease stages. Our analysis revealed aberrant DNA methylation at specific gene promoters in AT2 during COPD, which was anti-correlated with gene expression changes. Interferon signaling was the top-upregulated pathway in COPD associated with a concomitant loss of promoter-proximal DNA methylation. Integrated pathway analysis revealed transcription factor IRF9 as the master regulator of interferon signaling in COPD.

SUBMITTER: Maria Llamazares Prada 

PROVIDER: S-SCDT-10_1038-S44321-026-00386-9 | biostudies-other |

REPOSITORIES: biostudies-other