Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis (ChIP-seq)

Proper lung function relies on precisely balanced numbers of specialized epithelial cell types that work together and are maintained in homeostasis. In this study we have described essential roles for the transcriptional regulators YAP and TAZ, which are key effectors of Hippo pathway signaling, in maintaining lung epithelial homeostasis. Phenotypes associated with Yap/Taz deletion include alveolar defects and a striking development of goblet cell metaplasia throughout the airways. Knockdown of YAP and TAZ in HBECs similarly drives mucin expression. The TEAD family of transcription factors are well characterized partners of the YAP/TAZ transcriptional effectors, and we have found that knockdown of TEAD1-4 similarly drives elevated mucin expression. In order to further understand the role of the TEAD transcription factors in human lung epithelial cell fate, we conducted TEAD Chromatin Immunopreciptitation (ChIP)-Sequencing. Overall design: Examination of TEAD chromatin binding profiles in human bronchial epithelial cells. HBECs were cultured to high density in Pneumacult EX plus before ChIP Seq analysis. Cells were crosslinked via ethylene glycol bis (succinimidyl succinate) (EGS) and formaldehyde. Chromatin was sheared by sonication and immunoprecipitated with TEAD antibody (AvivaSystemsBiology).