Epithelial NELF guards intestinal barrier function to ameliorate colitis by maintaining junctional integrity.

ABSTRACT: Well-orchestrated transcriptional programs in intestinal epithelial cells (IECs) are essential for maintenance of optimal mucosal barrier functions, whereas the contribution of elongation-related mechanisms to barrier function remains unknown. Here, a combination of genetic and genomic approaches defined a critical role of IEC-intrinsic negative elongation factor (NELF) complex in maintenance of epithelial homeostasis. By direct occupancy at endogenous gene loci, NELF sustained expression of a subset of genes related to junctional integrity. As a result, epithelial NELF deficiency results in subdued levels of these junction-related genes and excessive IEC necroptosis in vivo secondary to commensal microbial invasion. In a colitis model, NELF-deficient mice exhibited severely impaired barri

SUBMITTER: Ou J 

PROVIDER: S-EPMC8881342 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature