The role of transcriptional regulators in maintaining lung function by controlling epithelial cell differentiation

The Mediator complex with its catalytic subunit the Mediator kinase module, composed of CDK8/19 and other members, is multimeric complex regulating the transcription machinery, transcription factor activity at promoter and enhancer regions and the chromatin landscape, thus controlling gene expression and cell lineage differentiation. While CDK8 and CDK19 are commonly dysregulated in cancers, we recently discovered that they are essential to maintain lung function. Using a series of genetically modified mouse models, innovative organoid cultures combined with state of the art omic approaches such as RNA-seq, ATAC-seq and Cut&Run, we will define the functions of Mediator kinases during differentiation of lung epithelial cells and their contribution to lung pathologies such as chronic obstructive pulmonary disease (COPD).