Thymic epithelial cells amplify epigenetic noise to promote immune tolerance.

ABSTRACT: Cellular plasticity is a principal feature of vertebrate adaptation, tissue repair and tumorigenesis^1,2. However, the mechanisms that regulate the stability of somatic cell fates remain unclear. Here, we use the somatic plasticity of thymic epithelial cells, which facilitates the selection of a self-discriminating T cell repertoire³, as a physiological model system to show that fluctuations in background chromatin accessibility in nucleosome-dense regions are amplified during thymic epithelial maturation for the ectopic expression of genes restricted to other specialized cell types. This chromatin destabilization was not dependent on AIRE-induced transcription but was preceded by repression of the tumour suppressor p53. Augmenting p53 activity indirectly stabilized ch

SUBMITTER: Gamble N 

PROVIDER: S-EPMC12527919 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature