With major progress being made in tissue engineering and organ regeneration, it is important to understand how the expression of genes in stem cells leads to their development into specialised cell types. Skin epithelium is a self-renewing biological structure that consists of the stem cells residing in the basal layer and differentiating into keratinocytes of suprabasal layers. This process results in a formation of an epidermal barrier protecting organisms from harmful environmental factors and is accompanied by activation of a number of epidermis-specific genes, located in the genome as clusters on four distinct chromosomes. However, it is unclear how these clusters are distributed in the nuclei of epidermal cells and what regulates their intra-nuclear arrangements and activity. We will test whether this process is regulated by a specific Satb1 protein that intergrates remodeling of large chromatin domains with regulation of gene expression. This project will shed light on the mechanisms that control gene reorganisation in the nuclei of epidermal cells and will be useful for better understanding the principles of stem cell-driven organ regeneration. Success of this project will be important for the progress in establishing new approaches in stem cell-based therapy and regenerative medicine.