What question did this study set out to answer?

To elucidate the genomic mechanisms and chromatin interactions that drive glucocorticoid-mediated induction of the transcription factor KLF9 in pulmonary epithelial cells.

November 13, 2020Journal of Biological ChemistryOpen Access

Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells

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Authors

MMMahmoud MostafaUniversity of Calgary ABAkanksha BansalUniversity of Calgary AMAubrey N. MichiSalk Institute for Biological Studies

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Implication

Laboratory study reveals how glucocorticoid receptor binding sites coordinate KLF9 induction in pulmonary epithelial cells, highlighting conserved transcriptional mechanisms in airway biology.

Key Points

To elucidate the genomic mechanisms and chromatin interactions that drive glucocorticoid-mediated induction of the transcription factor KLF9 in pulmonary epithelial cells.
Measured KLF9 expression in human airways in vivo, primary human bronchial epithelial (HBE) cells in submersion and air-liquid interface cultures, and A549 and BEAS-2B cell lines.
Identified regulatory elements using ChIP-seq, global run-on sequencing (GRO-seq), chromosome conformation capture to assess looping, and reporter gene assays with glucocorticoid response element (GRE) mutations.
Evaluated the functional requirement of transcriptional coactivators via CBP/P300 silencing.
ChIP-seq identified four conserved glucocorticoid receptor binding sites (GBSs)—two proximal and two distal to the transcription start site—which generate enhancer RNA upon glucocorticoid stimulation across primary cells and cell lines.
Distal GBSs required intact GREs to drive hormone-induced reporter activity, whereas the proximal GBS region mediated basal enhancer RNA production, RNA polymerase II enrichment, and pre-existing looping to the transcription start site.
Glucocorticoid treatment enhanced physical interactions between distal GBSs, proximal GBSs, and the transcription start site in tandem with KLF9 induction, while CBP/P300 silencing minimally affected KLF9 expression.

Cite This Study

Mostafa et al. (2020) studied this question.

synapsesocial.com/papers/6a8962a1d89205768aeb24da https://doi.org/10.1074/jbc.ra120.015755

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Implication

Laboratory study reveals how glucocorticoid receptor binding sites coordinate KLF9 induction in pulmonary epithelial cells, highlighting conserved transcriptional mechanisms in airway biology.

Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells

Discussion

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Implication

Key Points

Cite This Study

Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells

Discussion

Member takes

Implication

Key Points

Cite This Study

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