The Cohesin Complex Is Necessary for Epidermal Progenitor Cell Function through Maintenance of Self-Renewal Genes

Abstract

Adult stem and progenitor cells are critical for replenishing lost tissue due to injury or normal turnover. How these cells maintain self-renewal and sustain the tissue they populate are areas of active investigation. Here, we show that the cohesin complex, which has previously been implicated in regulating chromosome segregation and gene expression, is necessary to promote epidermal stem and progenitor cell self-renewal through cell-autonomous mechanisms. Cohesin binds to genomic sites associated with open chromatin, including DNase-I-hypersensitive sites, RNA polymerase II, and histone marks such as H3K27ac and H3K4me3. Reduced cohesin expression results in spontaneous epidermal differentiation due to loss of open chromatin structure and expression of key self-renewal genes. Our results demonstrate a prominent role for cohesin in modulating chromatin structure to allow for enforcement of a stem and progenitor cell gene expression program.