NIAMS-supported scientists at the Veterans Affairs Healthcare System in Palo Alto and at Stanford University have discovered a mechanism that contributes to differentiation of skin cells during normal skin growth. Understanding the processes that regulate normal skin growth may provide a better understanding of and lead to the development of therapies for diseases such as eczema and skin cancer. The study appeared in a recent issue of the journal Genes & Development.

Lead researcher, Paul A. Khavari, M.D., Ph.D., and his colleagues found that a specifically modified histone — a protein that interacts with DNA to regulate gene expression — represses the expression of some genes that are associated with differentiation of immature skin cells, resulting in the development of a specific type of mature skin cell. These mature skin cells migrate to the upper layers of the skin. This state of inhibition remains in place until an enzyme removes the modification, allowing the cell to mature. The researchers found that normal skin growth and maintenance depend upon the intricate balance of inhibition and activation of differentiation genes, regulated by the modified histone 3 Lysine 27 (H3K27me3) and the enzyme that removes the modification, Jumanjii C domain-containing protein (JMJD3).

The human skin growth process starts in the basal layer, where stem cells, the kind of cells that could become almost anything in our bodies, begin to change and migrate outward in four distinct stages, making up four skin layers. The researchers looked at keratinocytes, the main type of cell found in the epidermis — the outer layer of human skin. These skin cells are constantly replenishing themselves. In humans, the epidermal layer is completely replaced about every four weeks. Unlike reptiles, which keep their skin for a long time and then lose it all at once, we are continuously sloughing off dead cells and replacing them with new cells.

The proper balance between skin cell growth and differentiation, to form an effective barrier layer, is important for the health of the skin. Uncontrolled growth is a hallmark of skin cancer and defects in the skin barrier layer are often associated with diseases such as eczema and asthma. This study helps understand the role of epigenetics in the regulation of the growth and differentiation of the skin which may lead to new targets for drug development for these diseases.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at


Sen GL, Webster DE, Barragan DI, Chang HY, Khavari PA. Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3. Genes and Dev. 2008 Jul15;22(14):1865-70. PMID: 18628393

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