Control of the epithelial stem cell epigenome: the shaping of epithelial stem cell identity

The squamous epithelium covering the skin and oral mucosa relies on epithelial stem cells for tissue renewal. Dynamic changes in DNA methylation, histone methylation and acetylation, and higher order chromatin structure are required to preserve their self-renewal capacity while orchestrating the timely execution of cell differentiation programs. This complex network of epigenetic modifications shapes the epithelial stem cell identity and fate. Pathological alterations can be perceived by aberrant chromatin sensors, such as the INK4/ARF locus, which initiate tumor suppressive cell senescence programs, and can often result in epithelial stem cell exhaustion. Unveiling the mechanisms controlling the epigenome in epithelial stem cells may help protect against the loss of their tissue regenerative capacity, thereby preventing premature aging without increasing cancer risk.

► The skin and oral mucosa rely on epithelial stem cells for tissue renewal.
► Epigenetic modifications shape the identity of the epithelial stem cells.
► The regulation and properties of DNA and histone epigenetic marks are discussed.
► Cell stress conditions perturb the epigenetic networks in epithelial stem cells.
► The INK4/ARF locus acts as a sensor of aberrant chromatin status.